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Enhancing intervertebral disc repair and regeneration through biology: platelet-rich plasma as an alternative strategy


Intervertebral disc degeneration (IDD) is a common orthopedic disease associated with mechanical changes that may result in significant pain. Current treatments for IDD mainly depend on conservative therapies and spinal surgeries that are only able to relieve the symptoms but do not address the cause of the degeneration and even accelerate the degeneration of adjacent segments. This has prompted research to improve our understanding of the biology of intervertebral disc healing and into methods to enhance the regenerative process. Recently, biological therapies, including active substances, gene therapy and tissue engineering based on certain cells, have been attracting more attention in the field of intervertebral disc repair and regeneration. Early selection of suitable biological treatment is an ideal way to prevent or even reverse the progressive trend of IDD. Growth factors have been enjoying more popularity in the field of regeneration of IDD and many have been proved to be effective in reversing the degenerative trend of the intervertebral disc. Identification of these growth factors has led to strategies to deliver platelet-derived factors to the intervertebral disc for regeneration. Platelet-rich plasma (PRP) is the latest technique to be evaluated for promoting intervertebral disc healing. Activation of the PRP leads to the release of growth factors from the α-granules in the platelet cytoplasm. These growth factors have been associated with the initiation of a healing cascade that leads to cellular chemotaxis, angiogenesis, synthesis of collagen matrix, and cell proliferation. This review describes the current understanding of IDD and related biological therapeutic strategies, especially the promising prospects of PRP treatment. Future limitations and perspectives of PRP therapy for IDD are also discussed.


Intervertebral disc degeneration (IDD) is considered to be one of the strongly associated causes of lower back pain and related diseases of the spine, which exert a high cost on society [1, 2]. It is well known, however, that the intervertebral disc is an avascular tissue that has limited capacity for regeneration. This has prompted research to improve our understanding of the biology of intervertebral disc healing and into methods to enhance the regenerative process. Recently, biological treatments for early intervention have been introduced and developed, including the application of active substances, gene therapy and tissue engineering based on stem cells. These treatments have been reported to promote intervertebral disc regeneration by upregulating the synthesis of extracellular matrix and the metabolism of the intervertebral discs, further shedding light on the reversal and repair of IDD [3, 4].

The most direct therapeutic strategy for reversing IDD is the injection of active substances, mainly including multiple biologically active growth factors. As it contains high concentrations of platelets, which can release various kinds of multifunctional growth factors when activated (Table 1), platelet-rich plasma (PRP) represents a new strategy for the biological treatment of IDD [5]. Current studies have indicated that a variety of cytokines applied in the early stage of IDD could lead to a good outcome, as a large number of phenotypically stable cells are still present and could still react to these cytokines in the early degenerated discs. In addition, the combined application of multiple cytokines released from PRP will contribute to synergistic effects. This review explores the current biological therapeutic strategies for IDD and PRP as an autologous blood product used in the treatment of IDD. This survey and discussion might serve as a source of information to aid future applications of PRP and the design of appropriate biological strategies for treating human IDD.

Table 1 Growth factors identified within platelet-rich plasma and their biological functions

What is intervertebral disc degeneration?

IDD is perhaps best defined as a cascade that begins with changes to the cellular microenvironment and progresses to the structural breakdown and functional impairment of the intervertebral disc [6]. Aging, living conditions, biomechanical loading and genetic factors are often related to disc degeneration [7, 8]. Prominent changes occurring during IDD are characterized by a decrease of active cell numbers, depletion of extracellular matrix, altered phenotype of normal disc cells, and the presence of pro-inflammatory cytokines and mediators [9, 10]. These cellular and molecular changes greatly influence the progression of IDD, which further impairs the biological and mechanical function of the intervertebral disc and patients’ quality of life.

Current clinical treatments for intervertebral disc degeneration and their limitations

Current therapeutic strategies for treating IDD are primarily conservative, including physiotherapy and anti-inflammatory medications. Spinal surgery, mainly including discectomy, interbody fusion and disc replacement, are the current gold standard to alleviate symptoms of IDD, but the adjacent spine may experience a high risk of accelerated degeneration [11]. Therefore, the choice of an effective treatment for IDD with minimal adverse effects on individuals is particularly important to prevent the degenerative trend of IDD and relieve pain in patients.

Current status of biological treatments for intervertebral disc degeneration

With our improving understanding of the importance of the molecular and cellular mechanisms of IDD, biological treatments are attracting more attention [12, 13]. Promising biological treatments predominantly consist of direct injection of active substances, gene therapy and tissue engineering based on certain cells.

Direct injection of active substances could stimulate the proliferation of intervertebral disc cells and the accumulation of extracellular matrix [14], which could slow or even reverse the degenerative trend of IDD. However, the short half-life of active substances hinders the effectiveness of this therapy. So the ideal approach is to transfect intervertebral disc cells with genes encoding the active proteins so that these cells could stably produce the corresponding bioactive products, thus upregulating the synthesis of extracellular matrix in a gradual way. Tissue engineering using cells, especially stem cells, is based on the fact that the increase in active cells within the intervertebral disc will gradually restore its structural integrity and function; many studies have confirmed the efficacy of this procedure [1517]. Carriers or scaffolds of stem cells with good bio-compatibility are currently being developed with promising prospects.

However, studies on biological treatments for IDD have so far mostly been restricted to in vitro studies and animal experiments, and clinical application is still a long way in the future. According to current experimental results, biological treatments hold broad prospects for preventing or even reversing the progression of IDD.

Biological and pathological characteristics of intervertebral disc degeneration: the importance of and opportunities for early interventions

With the lack of nutrient diffusion through the cartilaginous endplate, degenerated intervertebral discs may undergo a gradual decrease in active cell numbers [18]. Also, the degenerative process of the intervertebral disc is significantly related to the loss of proteoglycan, which further lowers the osmotic pressure of the internal environment and renders the degenerated disc unable to maintain hydration under load [19]. Although collagen content decreases with the progression of IDD, this is not significant compared to that of proteoglycans. However, a shift in the balance of collagen types and their distribution may occur. The decrease in collagen content and the shift from type II to type I collagen contribute to fibrosis of the nucleus pulpous [20]. With the fusion of the nucleus pulposus and annulus fibrosis, the difference between the two becomes less obvious.

IDD is a progressive, chronic disease. Over time, the degeneration worsens and ultimately becomes irreversible, so early biological intervention is important to reverse the trend of degeneration [21]. In the late stage of IDD, the calcified cartilage endplates (CEPs) hold limited potential for vascularization and nutrient delivery. Early intervention during disc degeneration has many advantages because many viable cells are still retained and cellular phenotypic changes are few. So the injection of active substances is potent enough to stimulate restoration during the early stage of degeneration. Early in IDD, single or multiple injections of biologically active substances, especially growth factors, could effectively regulate the metabolic balance of the extracellular matrix and maintain the homeostasis of the intervertebral disc [22]. Gene therapy [23, 24] and tissue engineering based on stem cells [25, 26] are possible alternative choices for IDD therapy. Gene therapy could prolong the duration of expression of active substances but the efficacy of clinical application and safety issues have not yet been determined. Tissue engineering based on cells requires a high standard of clinical research, complicated culture conditions, as well as complex surgical procedures. Meanwhile, the existence of immune rejection, tumorigenicity of the transplanted cells, and unexpected outcomes restrict the prospects for their clinical application. Therefore, the ideal solution to prevent or even reverse the degenerative trend of IDD is intervention using active substances in the early stage of IDD.

Effects of platelet-rich plasma growth factors on intervertebral disc degeneration: in vitro and in vivo studies

The injection of active substances is more suitable for early intervention in IDD compared with other therapies. Stimulation from active substances, especially the cytokines or growth factors present in PRP, maintains intervertebral disc homeostasis by shifting cellular catabolism to the anabolic state [27]. The clinical injection of active substances can be carried out under fluoroscopic guidance and is less invasive than spinal surgeries, especially for multi-segment disc degeneration, reducing injury to a minimum level.

Many in vivo and in vitro studies have been conducted using multiple growth factors present in PRP to stimulate the proliferation of intervertebral disc cells with promising results (Table 2). Transforming growth factor (TGF)-β1 is one of the early morphogenic molecules studied in vitro to promote the synthesis of proteoglycans [28, 29]. Gruber and colleagues [30] reported that TGF-β1 could effectively stimulate the proliferation of human annulus fibrosus cells after 4 days exposure. Lee and colleagues [31] confirmed the proliferative effect of TGF-β1 when culturing rabbit nucleus pulposus cells seeded in atelocollagen scaffolds under the stimulation of TGF-β1. Insulin-like growth factor (IGF)-1 has a similar function as it promotes cell proliferation and matrix synthesis in vitro[32]. A study from Hayes and Ralphs [33] confirmed that TGF-β1 and IGF-1, both alone and in combination, could effectively stimulate the synthesis of sulfated glycosaminoglycan and collagen types I and II by annulus cells. Further, these authors proved the potential role of TGF-1 in pushing cells towards a fibrocartilaginous phenotype, with possible complementary effects of IGF-1. In addition, IGF-1 and platelet-derived growth factor (PDGF) were both reported to be able to reduce the percentage of apoptotic annulus fibrosus cells [34]. However, another study indicated that TGF-β was superior to epidermal growth factor (EGF), IGF-1, PDGF and fibroblastic growth factor (FGF) in upregulating the synthesis of proteoglycan [32].

Table 2 The in vitro and in vivo influence of growth factors present in platelet-rich plasma

In an in vitro culture system, Pratsinis and Kletsas [35] reported that PDGF, basic FGF (bFGF) and IGF-I could all effectively stimulate the proliferation of intervertebral disc cells obtained from bovine coccygeal tissues, and PDGF was the most potent mitogen among these. Vascular endothelial growth factor (VEGF)-A functions in nucleus pulposus survival as it has strong angiogenic activity and specific mitogenic and chemotactic actions [36]. In a gene transfection study, Liu and colleagues [37] reported that the increased connective tissue growth factor (CTGF) expression resulting from transfecting rAAV2-CTGF into Rhesus monkey lumbar nucleus pulposus cells enhanced collagen type II protein and proteoglycan synthesis. In a degenerative murine caudal disc compression model, Walsh and colleagues [38] compared the effects of single and multiple injections of a variety of growth factors, including growth and differentiation factor (GDF)-5, TGF-β, IGF-1, and bFGF; GDF-5 and TGF-β induced the expansion of the inner annulus fibrosus fibrochondrocyte populations into the nucleus pulposus and upregulated the expression of aggrecan and type II collagen, while IGF-1 yielded a transient proliferative effect. The authors thus concluded that early intervention during disc degeneration had implications for the arrest or slowing of the degenerative process.

Given the interactions of growth factors that are necessary for proper intervertebral disc homeostasis and regeneration, it is unlikely that any single growth factor will alone enable the repair of IDD, but rather a combination of multiple growth factors will be needed. Based on the concept that a combination approach is necessary for disc regeneration, recent attention has turned to PRP.

Platelet-rich plasma as a strategy for intervertebral disc degeneration repair and regeneration

PRP can be defined as a volume of autologous plasma with the platelet concentration above baseline [39]. PRP has been clinically applied for its healing properties [40], and now is widely applied in many therapeutic areas. The concept that PRP application would promote IDD regeneration is based on the role of platelets in wound healing. When activated, platelets can secrete a variety of growth factors, including PDGF, IGF-1, TGF-β, VEGF, bFGF, EGF, and CTGF, among others [41, 42]. All these growth factors might play significant roles in promoting the proliferation of tissues. Platelets also contain antibacterial and bactericidal proteins that may influence the process of inflammatory responses by inducing the synthesis of some molecules, such as integrins, interleukins and chemokines [43]. Last but not least, platelets may serve as a biological sponge because they can absorb, store and transfer some small molecules that regulate tissue regeneration [44]. PRP represents a new biotechnology in tissue engineering and has become a popular clinical treatment for various tissue healing applications without any immune rejections.

Compared with other bioactive peptides or growth factors, however, PRP is limited in its clinical application mainly because of its autologous origin. If the physical condition of a patient renders them unsuitable for generating PRP, such as patients with hematologic diseases, then PRP will not be an ideal therapy for IDD. Modern biotechnology has greatly increased our knowledge about the gene sequences and receptors of many bioactive substances and although artificially synthesized growth factors are more costly with short half-lives, they are convenient and their application is not restrained by the physical condition of the patient.

Compared with other bioactive factors, PRP is rather a good choice for patients qualified for PRP preparations. Unlike other bioactive factors with complicated or unstable properties used for the clinical treatment of damaged tissues, PRP can be quickly obtained in the operating room by centrifugation of the patient’s own blood and directly applied to target tissues. Also, from the viewpoint of clinical application, autologous PRP avoids complex regulations, disease transmission and immunologic reactions [45].

PRP injection into degenerated intervertebral discs is currently a relatively less invasive and convenient therapeutic procedure compared to other options. However, needle puncture could induce cell death and degeneration of discs [4648], so needles of smaller size and the fewest numbers of injections possible are beneficial for clinical patients. To the best of our knowledge, no clinical studies have so far indicated the number of injections required. Some preclinical studies have indicated that a single injection of PRP in the degenerated discs of animal models was effective to help restore disc height and water content [4648]. Gullung and colleagues [46] confirmed that a single injection of PRP into the degenerated discs of Sprague–Dawley rats was effective for maintaining fluid content on magnetic resonance imaging (MRI). Obata and colleagues [47, 48] proved that a single intra-discal injection of PRP serum was potent enough to restore disc height and induce cell proliferation in a rabbit IDD model. In our previous animal study, which established an early IDD model, a single injection of PRP was effective for IDD regeneration [49].

Considering these animal studies, we propose that a single injection using smaller needles at the right time, especially in the early stage of IDD, might be sufficient for clinical applications. However, more clinical studies are needed in the future to confirm this.

Current evidence for the efficacy of platelet-rich plasma therapy in intervertebral disc degeneration

PRP contains a variety of proteins and growth factors that are expected to serve as a therapeutic growth factor cocktail, playing a pivotal role in regulating the tissue microenvironment, improving cellular functions and promoting the regeneration of damaged tissues. Many in vivo and in vitro studies have confirmed the efficacy of PRP in IDD treatment (Table 3).

Table 3 In vitro and in vivo effects of platelet-rich plasma on intervertebral disc regeneration

Chen and colleagues [50] demonstrated that PRP might be a therapeutic candidate for the prevention of IDD by culturing intervertebral disc cells together with PRP. Subsequently, Chen and colleagues [51] introduced a novel intervertebral disc organ culture system to study a PRP-based therapeutic approach for the amelioration of IDD. Their results indicated that PRP could promote nucleus pulposus regeneration and resulted in significantly increased levels of mRNAs involved in chondrogenesis and matrix accumulation; moreover, the disc height index was significantly increased in the PRP regeneration groups.

A study from Akeda and colleagues [52] demonstrated that PRP had a mild stimulatory effect on the proliferation of intervertebral disc cells. The authors concluded that the local administration of PRP might stimulate intervertebral disc repair, and autologous blood would be favored as a source of growth factors needed to stimulate cells for tissue engineering of the intervertebral disc. However, the injected PRP within intervertebral discs might release growth factors in an unstable manner at different rates. To slow the release of biological factors within PRP, Nagae and colleagues [53] used a combination therapy of PRP implanted within gelatin hydrogel microspheres on a rabbit IDD model. The immobilized PRP released PRP-related growth factors in a sustained manner with the degradation of the microspheres, and the degeneration of intervertebral discs was remarkably suppressed over the 8-week period in the PRP group. The authors suggested that the combined administration of PRP and gelatin hydrogel microspheres may serve as a promising therapeutic strategy for IDD. This study was advanced by Sawamura and colleagues [54], the authors further confirming the efficacy of PRP impregnated within gelatin hydrogel microspheres to retard the degenerative trend. Gullung and colleagues [46] compared the regenerative effects of early PRP injection and delayed PRP injection in a rat IDD model induced by needle puncture of Sprague–Dawley rats. Both early and delayed PRP intervention resulted in higher fluid content on MRI, and the disc was superior in the early PRP injection group. Obata and colleagues [47, 48] demonstrated that intra-discal injection of PRP serum was effective for restoring disc height and promoting cell proliferation in a rabbit model, and further held that PRP is safe and immediately available for clinical application. Recently, a study from our group confirmed that a single injection of PRP was potent enough to increase the production of extracellular matrix and maintained the MRI signal intensity of degenerated discs in a rabbit model [49]. All these studies offer a promising option for the regeneration of IDD compared with the traditional, conservative therapies and ultimate surgery, and indicate that PRP could effectively stimulate the restoration of degenerated intervertebral discs via the proliferative effects of multiple growth factors secreted from the platelets.

Possible mechanism of the therapeutic effect of platelet-rich plasma in intervertebral disc degeneration

Platelets have exhibited greater therapeutic potential than ever imagined, releasing growth factors and other molecules that help to repair damaged tissues [55]. Over 1,500 proteins are stored within platelets, including growth factors in platelet α-granules that have been proven to promote normal healing responses [56, 57]. PRP, as a source of concentrated platelets, may help to restore the integrity of the cellular matrix of degenerating discs through the synergistic effects of multiple growth factors.

The balance between decomposition and accumulation determines the integrity and mechanical behavior of discs. Thus, increased extracellular matrix, mainly including aggrecan and collagen, helps to maintain the mechanical functions of the discs. Aggrecan, the major proteoglycan, is rich in negatively charged sulfate and carboxyl groups, contributing to high osmotic pressure for the absorption of water [19, 58, 59]. The increased collagen provides tensile strength and anchors the tissue to the bone [19].

As an aneural and avascular tissue, the intervertebral disc derives nutrients and oxygen from two thin CEPs [60]. During the progression of IDD, the calcification of the CEPs is accompanied by the obliteration of the small blood vessels [61]. This was supposed to be one of the causes of IDD. In degenerating discs, however, blood vessels were found in the endplates and subchondral bone, which may imply that vascularization was strongly associated with tissue repair [62, 63]. Based on this understanding, VEGF released from PRP is a potent cytokine for vascularization within the CEP, promoting the diffusion of nutrients to the degenerated discs. The synthesis of integrins and interleukins induced by the platelets will spark the inflammatory response and alert immune cells [43, 44]. As the apoptosis of chondrocytes within the CEP is believed to be an important cause of IDD, PRP-derived growth factors, such as TGF-β, IGF, and FGF may restore the degenerated CEP by promoting cell growth and tissue regeneration.

Although new vessel formation would help to re-establish nutritive perfusion during the process of wound healing [64, 65], the enhanced neovascularization is associated with severe histodegeneration of the discs. Also, the local vascular inflammatory reactions resulting from the synthesis of integrins and interleukins may be the main cause of the painful disc fibrosis and degeneration [66]. Degeneration in discs is associated with increases in the number of nerves and blood vessels [67]. Thus, along with the advantage of better nutrient supply induced by PRP, there is the possible disadvantage of significant pain and calcification through the process of inflammation. Therefore, further studies are still needed to investigate the undesirable effects induced by PRP.

Some studies have indicated that a certain number of mesenchymal stem cells (MSCs) exist in human degenerated intervertebral discs, including the CEP, nucleus pulposus and annulus fibrosus tissues [6871], although none reported whether PRP affects the proliferation and differentiation of these specialized MSCs. But a study on the influence of PRP on human MSCs has proved that PRP enhanced MSC proliferation and induced chondrogenic differentiation of MSCs in vitro[72]. Stem cells derived from tendon also showed a trend to proliferate and differentiate toward activated tenocytes when cultured with PRP [73]. Therefore, we further propose that PRP, as a growth factor cocktail, might stimulate the differentiation of intervertebral disc MSCs towards mature intervertebral disc cells and upregulate the synthesis of extracellular matrix, and finally slow or reverse the degenerative trend of IDD.

Limitations of the current evidence on the application of platelet-rich plasma therapy and directions of future research

PRP has demonstrated efficacy when used as a culture supplement for tissue engineering, as well as in promoting the biological regeneration of degenerated intervertebral discs. Currently, most findings indicate that PRP could serve as a potential therapeutic candidate to facilitate biological disc repair. However, some problems need to be resolved before the clinical application of PRP for the treatment of IDD. Currently, the pathological mechanism of IDD is still unclear, and current studies further indicate that a certain number of MSCs inhabit degenerated human nucleus pulposus. So, further studies are required to clarify the impact of PRP on the proliferation and differentiation of the nucleus pulposus-derived stem cells. PRP produced by different procedures may lead to varying degrees of platelet destruction, resulting in different concentrations of growth factors. Furthermore, as no uniform standard has been determined for stable PRP production, quality assurance of PRP should be taken into serious consideration. In addition, the optimal doses of various growth factors in PRP for tissue regeneration and the interactions between the different growth factors remain to be elucidated. Clinical PRP applications are currently focused on maxillofacial tissue engineering while clinical data for PRP therapy in IDD are still insufficient. The mechanism of IDD together with the roles of PRP in treating it are focal points of future research.



Cartilage endplate


Connective tissue growth factor


Epidermal growth factor


Fibroblastic growth factor


Growth and differentiation factor


Intervertebral disc degeneration


Insulin-like growth factor


Magnetic resonance imaging


Mesenchymal stem cell


Platelet-derived growth factor


Platelet-rich plasma


Transforming growth factor


Vascular endothelial growth factor.


  1. 1.

    Frymoyer JW, Cats-Baril WL: An overview of the incidence and costs of low back pain. Orthop Clin North Am. 1991, 22: 263-271.

    CAS  PubMed  Google Scholar 

  2. 2.

    Shvartzman L, Weingarten E, Sherry H, Levin S, Persaud A: Cost-effectiveness analysis of extended conservative therapy versus surgical intervention in the management of herniated lumbar intervertebral disc. Spine. 1992, 17: 176-182.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    An HS, Thonar EJ, Masuda K: Biological repair of intervertebral disc. Spine. 2003, 28: S86-S92.

    Article  PubMed  Google Scholar 

  4. 4.

    Evans C: Potential biologic therapies for the intervertebral disc. J Bone Joint Surg Am. 2006, 88: 95-98.

    Article  PubMed  Google Scholar 

  5. 5.

    Pietrzak WS, Eppley BL: Platelet rich plasma: biology and new technology. J Craniofac Surg. 2005, 16: 1043-1054.

    Article  PubMed  Google Scholar 

  6. 6.

    Freemont AJ: The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. Rheumatology. 2009, 48: 5-10.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Choi YS: Pathophysiology of degenerative disc disease. Asian Spine J. 2009, 3: 39-44.

    PubMed Central  Article  PubMed  Google Scholar 

  8. 8.

    Schoenfeld AJ, Nelson JH, Burks R, Belmont PJ: Incidence and risk factors for lumbar degenerative disc disease in the United States military 1999-2008. Mil Med. 2011, 176: 1320-1324.

    Article  PubMed  Google Scholar 

  9. 9.

    Singh K, Masuda K, An HS: Animal models for human disc degeneration. Spine J. 2005, 5: 267S-279S.

    Article  PubMed  Google Scholar 

  10. 10.

    Adams MA, Roughley PJ: What is intervertebral disc degeneration, and what causes it?. Spine. 2006, 31: 2151-2161.

    Article  PubMed  Google Scholar 

  11. 11.

    Karppinen J, Shen FH, Luk KD, Andersson GB, Cheung KM, Samartzis D: Management of degenerative disk disease and chronic low back pain. Orthop Clin North Am. 2011, 42: 513-528.

    Article  PubMed  Google Scholar 

  12. 12.

    Sakai D: Future perspectives of cell-based therapy for intervertebral disc disease. Eur Spine J. 2008, 17: 452-458.

    PubMed Central  Article  PubMed  Google Scholar 

  13. 13.

    Yoon ST, Patel NM: Molecular therapy of the intervertebral disc. Eur Spine J. 2006, 15: S379-S388.

    Article  PubMed  Google Scholar 

  14. 14.

    Masuda K, An HS: Prevention of disc degeneration with growth factors. Eur Spine J. 2006, 15: S422-S432.

    Article  PubMed  Google Scholar 

  15. 15.

    Crevensten G, Walsh AJ, Ananthakrishnan D, Page P, Wahba GM, Lotz JC, Berven S: Intervertebral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng. 2004, 32: 430-434.

    Article  PubMed  Google Scholar 

  16. 16.

    Hiyama A, Mochida J, Iwashina T, Omi H, Watanabe T, Serigano K, Tamura F, Sakai D: Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res. 2008, 26: 589-600.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Zhang YG, Guo X, Xu P, Kang LL, Li J: Bone mesenchymal stem cells transplanted into rabbit intervertebral discs can increase proteoglycans. Clin Orthop Relat Res. 2005, 430: 219-226.

    Article  PubMed  Google Scholar 

  18. 18.

    Lyons G, Eisenstein SM, Sweet MB: Biochemical changes in intervertebral disc degeneration. Biochim Biophys Acta. 1981, 673: 443-453.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Urban JP, Roberts S: Degeneration of the intervertebral disc. Arthritis Res Ther. 2003, 5: 120-130.

    PubMed Central  Article  PubMed  Google Scholar 

  20. 20.

    Freemont AJ: The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. Rheumatology. 2009, 48: 5-10.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Yang SH, Lin CC, Hu MH, Shih TT, Sun YH, Lin FH: Influence of age-related degeneration on regenerative potential of human nucleus pulposus cells. J Orthop Res. 2010, 28: 379-383.

    PubMed  Google Scholar 

  22. 22.

    Masuda K: Biological repair of the degenerated intervertebral disc by the injection of growth factors. Eur Spine J. 2008, 17: 441-451.

    PubMed Central  Article  PubMed  Google Scholar 

  23. 23.

    Le Maitre CL, Freemont AJ, Hoyland JA: A preliminary in vitro study into the use of IL-1Ra gene therapy for the inhibition of intervertebral disc degeneration. Int J Exp Pathol. 2006, 87: 17-28.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  24. 24.

    Wallach CJ, Sobajima S, Watanabe Y, Kim JS, Georgescu HI, Robbins P, Gilbertson LG, Kang JD: Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs. Spine. 2003, 28: 2331-2337.

    Article  PubMed  Google Scholar 

  25. 25.

    Sakai D, Mochida J, Iwashina T, Watanabe T, Nakai T, Ando K, Hotta T: Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine. 2005, 30: 2379-2387.

    Article  PubMed  Google Scholar 

  26. 26.

    Zhang Y, Drapeau S, Howard SA, Thonar EJ, Anderson DG: Transplantation of goat bone marrow stromal cells to the degenerating intervertebral disc in a goat disc injury model. Spine. 2011, 36: 372-377.

    PubMed Central  PubMed  Google Scholar 

  27. 27.

    Masuda K, Oegema TR, An HS: Growth factors and treatment of intervertebral disc degeneration. Spine. 2004, 29: 2757-2769.

    Article  PubMed  Google Scholar 

  28. 28.

    Nishida K, Kang JD, Gilbertson LG, Moon SH, Suh JK, Vogt MT, Robbins PD, Evans CH: Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy: an in vivo study of adenovirus-mediated transfer of the human transforming growth factor beta 1 encoding gene. Spine. 1999, 24: 2419-2425.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Osada R, Ohshima H, Ishihara H, Yudoh K, Sakai K, Matsui H, Tsuji H: Autocrine/paracrine mechanism of insulin-like growth factor-1 secretion, and the effect of insulin-like growth factor-1 on proteoglycan synthesis in bovine intervertebral discs. J Orthop Res. 1996, 14: 690-699.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Gruber HE, Fisher EC, Desai B, Stasky AA, Hoelscher G, Hanley EN: Human intervertebral disc cells from the annulus: three-dimensional culture in agarose or alginate and responsiveness to TGF-beta1. Exp Cell Res. 1997, 235: 13-21.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Lee KI, Moon SH, Kim H, Kwon UH, Kim HJ, Park SN, Suh H, Lee HM, Kim HS, Chun HJ, Kwon IK, Jang JW: Tissue engineering of the intervertebral disc with cultured nucleus pulposus cells using atelocollagen scaffold and growth factors. Spine. 2012, 37: 452-458.

    Article  PubMed  Google Scholar 

  32. 32.

    Thompson JP, Oegema TR, Bradford DS: Stimulation of mature canine intervertebral disc by growth factors. Spine. 1991, 16: 253-260.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Hayes AJ, Ralphs JR: The response of foetal annulus fibrosus cells to growth factors: modulation of matrix synthesis by TGF-β1 and IGF-1. Histochem Cell Biol. 2011, 136: 163-175.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Gruber HE, Norton HJ, Hanley EN: Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro. Spine. 2000, 25: 2153-2157.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Pratsinis H, Kletsas D: PDGF, bFGF and IGF-I stimulate the proliferation of intervertebral disc cells in vitro via the activation of the ERK and Akt signaling pathways. Eur Spine J. 2007, 16: 1858-1866.

    PubMed Central  Article  PubMed  Google Scholar 

  36. 36.

    Fujita N, Imai J, Suzuki T, Yamada M, Ninomiya K, Miyamoto K: Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc. Biochem Biophys Res Commun. 2008, 372: 367-372.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Liu Y, Kong J, Chen BH, Hu YG: Combined expression of CTGF and tissue inhibitor of metalloprotease-1 promotes synthesis of proteoglycan and collagen type II in rhesus monkey lumbar intervertebral disc cells in vitro. Chin Med J (Engl). 2010, 123: 2082-2087.

    CAS  Google Scholar 

  38. 38.

    Walsh AJ, Bradford DS, Lotz JC: In vivo growth factor treatment of degenerated intervertebral discs. Spine. 2004, 29: 156-163.

    Article  PubMed  Google Scholar 

  39. 39.

    Marx RE: Platelet-rich plasma (PRP): what is PRP and what is not PRP?. Implant Dent. 2001, 10: 225-228.

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Sánchez-González DJ, Méndez-Bolaina E, Trejo-Bahena NI: Platelet-rich plasma peptides: key for regeneration. Int J Pept. 2012, 2012: 532519-

    PubMed Central  Article  PubMed  Google Scholar 

  41. 41.

    Brass L: Understanding and evaluating platelet function. Hematology Am Soc Hematol Educ Program. 2010, 2010: 387-396.

    Article  PubMed  Google Scholar 

  42. 42.

    Knighton DR, Hunt TK, Thakral KK, Goodson WH: Role of platelets and fibrin in the healing sequence: an in vivo study of angiogenesis and collagen synthesis. Ann Surg. 1982, 196: 379-388.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  43. 43.

    Fréchette JP, Martineau I, Gagnon G: Platelet-rich plasmas: growth factor content and roles in wound healing. J Dent Res. 2005, 84: 434-439.

    Article  PubMed  Google Scholar 

  44. 44.

    Leslie M: Cell biology. Beyond clotting: the powers of platelets. Science. 2010, 328: 562-564.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Marx RE: Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg. 2004, 62: 489-496.

    Article  PubMed  Google Scholar 

  46. 46.

    Gullung GB, Woodall JW, Tucci MA, James J, Black DA, McGuire RA: Platelet-rich plasma effects on degenerative disc disease: analysis of histology and imaging in an animal model. Evid Based Spine Care J. 2011, 2: 13-18.

    PubMed Central  Article  PubMed  Google Scholar 

  47. 47.

    Obata S, Akeda K, Morimoto R, Asanuma Y, Kasai Y, Masuda K, Uchida A, Sudo A: Intradiscal injection of autologous platelet-rich plasma-serum induces the restoration of disc height in the rabbit anular needle puncture model: 12 [abstract]. Spine Aff Soc Meeting Abstracts. 2010, 12:

    Google Scholar 

  48. 48.

    Obata S, Akeda K, Imanishi T, Masuda K, Bae W, Morimoto R, Asanuma Y, Kasai Y, Uchida A, Sudo A: Effect of autologous platelet-rich plasma-releasate on intervertebral disc degeneration in the rabbit anular puncture model: a preclinical study. Arthritis Res Ther. 2012, 14: R241-

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  49. 49.

    Hu X, Wang C: An experimental study on the effect of autologous platelet-rich plasma on treatment of early intervertebral disc degeneration. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2012, 26: 977-983.

    CAS  PubMed  Google Scholar 

  50. 50.

    Chen WH, Lo WC, Lee JJ, Su CH, Lin CT, Liu HY, Lin TW, Lin WC, Huang TY, Deng WP: Tissue-engineered intervertebral disc and chondrogenesis using human nucleus pulposus regulated through TGF-beta1 in platelet-rich plasma. J Cell Physiol. 2006, 209: 744-754.

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Chen WH, Liu HY, Lo WC, Wu SC, Chi CH, Chang HY, Hsiao SH, Wu CH, Chiu WT, Chen BJ, Deng WP: Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. Biomaterials. 2009, 30: 5523-5533.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Akeda K, An HS, Pichika R, Attawia M, Thonar EJ, Lenz ME, Uchida A, Masuda K: Platelet-rich plasma (PRP) stimulates the extracellular matrix metabolism of porcine nucleus pulposus and anulus fibrosus cells cultured in alginate beads. Spine. 2006, 31: 959-966.

    Article  PubMed  Google Scholar 

  53. 53.

    Nagae M, Ikeda T, Mikami Y, Hase H, Ozawa H, Matsuda K, Sakamoto H, Tabata Y, Kawata M, Kubo T: Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres. Tissue Eng. 2007, 13: 147-158.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Sawamura K, Ikeda T, Nagae M, Okamoto S, Mikami Y, Hase H, Ikoma K, Yamada T, Sakamoto H, Matsuda K, Tabata Y, Kawata M, Kubo T: Characterization of in vivo effects of platelet-rich plasma and biodegradable gelatin hydrogel microspheres on degenerated intervertebral discs. Tissue Eng. 2009, 15: 3719-3727.

    CAS  Article  Google Scholar 

  55. 55.

    Brass L: Understanding and evaluating platelet function. Hematology. Am Soc Hematol Educ Program. 2010, 2010: 387-396.

    Article  Google Scholar 

  56. 56.

    McNicol A, Israels SJ: Beyond hemostasis: the role of platelets in inflammation, malignancy and infection. Cardiovasc Hematol Disord Drug Targets. 2008, 8: 99-117.

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Rozman P, Bolta Z: Use of platelet growth factors in treating wounds and soft-tissue injuries. Acta Dermatovenerol Alp Panonica Adriat. 2007, 16: 156-165.

    CAS  Google Scholar 

  58. 58.

    Johnstone B, Bayliss MT: The large proteoglycans of the human intervertebral disc. Changes in their biosynthesis and structure with age, topography, and pathology. Spine. 1995, 20: 674-684.

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Urban JP, Maroudas A, Bayliss MT, Dillon J: Swelling pressures of proteoglycans at the concentrations found in cartilaginous tissues. Biorheology. 1979, 16: 447-464.

    CAS  PubMed  Google Scholar 

  60. 60.

    Urban JP, Smith S, Fairbank JC: Nutrition of the intervertebral disc. Spine. 2004, 29: 2700-2709.

    Article  PubMed  Google Scholar 

  61. 61.

    Moore RJ: The vertebral endplate: disc degeneration, disc regeneration. Eur Spine. 2006, 15: S333-S337.

    Article  Google Scholar 

  62. 62.

    Brown MF, Hukkanen MVJ, McCarthy ID, Redfern DRM, Batten JJ, Crock HV, Hughes SPF, Polak JM: Sensory and sympathetic innervation of the vertebral endplate in patients with degenerative disc disease. J Bone Joint Surg. 1997, 79: 147-153.

    CAS  Article  Google Scholar 

  63. 63.

    Fagan A, Moore R, Vernon Roberts B, Blumbergs P, Fraser R: The innervation of the intervertebral disc: a quantitative analysis. Spine. 2003, 28: 2570-2576.

    Article  PubMed  Google Scholar 

  64. 64.

    Gurtner GC, Werner S, Barrandon Y, Longaker MT: Wound repair and regeneration. Nature. 2008, 453: 314-321.

    CAS  Article  PubMed  Google Scholar 

  65. 65.

    Folkman J: Fundamental concepts of the angiogenic process. Curr Mol Med. 2003, 3: 643-651.

    CAS  Article  PubMed  Google Scholar 

  66. 66.

    Peng BG: Pathophysiology, diagnosis, and treatment of discogenic low back pain. World J Orthop. 2013, 4: 42-52.

    PubMed Central  Article  PubMed  Google Scholar 

  67. 67.

    David G, Ciurea AV, Iencean SM, Mohan A: Angiogenesis in the degeneration of the lumbar intervertebral disc. J Med Life. 2010, 3: 154-161.

    PubMed Central  PubMed  Google Scholar 

  68. 68.

    Liu LT, Huang B, Li CQ, Zhuang Y, Wang J, Zhou Y: Characteristics of stem cells derived from the degenerated human intervertebral disc cartilage endplate. PLoS One. 2011, 6: e26285-

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  69. 69.

    Henriksson H, Thornemo M, Karlsson C, Hägg O, Junevik K, Lindahl A, Brisby H: Identification of cell proliferation zones, progenitor cells and a potential stem cell niche in the intervertebral disc region: a study in four species. Spine. 2009, 34: 2278-2287.

    Article  PubMed  Google Scholar 

  70. 70.

    Blanco JF, Graciani IF, Sanchez-Guijo FM, Muntión S, Hernandez-Campo P, Santamaria C, Carrancio S, Barbado MV, Cruz G, Gutierrez-Cosío S, Herrero C, San Miguel JF, Briñon JG, del Cañizo MC: Isolation and characterization of mesenchymal stromal cells from human degenerated nucleus pulposus: comparison with bone marrow mesenchymal stromal cells from the same subjects. Spine. 2010, 35: 2259-2265.

    Article  PubMed  Google Scholar 

  71. 71.

    Risbud MV, Guttapalli A, Tsai TT, Lee JY, Danielson KG, Vaccaro AR, Albert TJ, Gazit Z, Gazit D, Shapiro IM: Evidence for skeletal progenitor cells in the degenerate human intervertebral disc. Spine. 2007, 32: 2537-2544.

    Article  PubMed  Google Scholar 

  72. 72.

    Mishra A, Tummala P, King A, Lee B, Kraus M, Tse V, Jacobs CR: Buffered platelet-rich plasma enhances mesenchymal stem cell proliferation and chondrogenic differentiation. Tissue Eng. 2009, 15: 431-435.

    CAS  Article  Google Scholar 

  73. 73.

    Zhang J, Wang JH: Platelet-rich plasma releasate promotes differentiation of tendon stem cells into active tenocytes. Am J Sports Med. 2010, 38: 2477-2486.

    Article  PubMed  Google Scholar 

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This work was supported by National Natural Science Foundation of China (grant no. 81201422), China Postdoctoral Science Foundation (grant no. 2012M520983), National Student Innovation Training Program of China (grant no. 1210286090), Jiangsu Province Science Foundation for Youths (grant no. BK2012334) and Innovative Foundation of Southeast University (grant no. 3290002401).

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Correspondence to Yun-Feng Rui or Chen Wang.

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The authors declare that they have no competing interests.

Shan-Zheng Wang, Yun-Feng Rui contributed equally to this work.

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Wang, S., Rui, Y., Tan, Q. et al. Enhancing intervertebral disc repair and regeneration through biology: platelet-rich plasma as an alternative strategy. Arthritis Res Ther 15, 220 (2013).

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  • Intervertebral Disc
  • Nucleus Pulposus
  • Connective Tissue Growth Factor
  • Nucleus Pulposus Cell
  • Intervertebral Disc Degeneration