Bone Marrow-derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis
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Published:
Apr 30, 2015
Keywords:
Knee Osteoarthritis Cell based therapy Mesenchymal stem cells
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Abstract
Forty percent of people over 70 years of age suffer from knee osteoarthritis. Stem cell based therapy is one of a number of promising strategies for osteoarthritis treatment. Mesenchymal stromal /stem cells (MSCs) derived from the bone marrow are the most commonly described source of MSCs and have been widely used to promote tissue regeneration in orthopaedic conditions, particularly in osteoarthritis. A fundamental knowledge of stem cells is very important prior to translating this technology into clinical practice. Although the mechanism of MSC therapy is still uncertain, several studies have reported on the safety and outcome of using bone marrow-derived MSCs for treating osteoarthritis. However, we still cannot conclude that MSCs can regenerate long lasting cartilage tissue. The long term clinical studies need to be evaluated in the future.
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References
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2. Dieppe PA, Lohmander LS. Pathogenesis and management of pain in osteoarthritis. Lancet 2005; 365: 965-73.
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4. Healy WL, Della Valle CJ, Iorio R, Berend KR, Cushner FD, Dalury DF, et al. Complications of total knee arthroplasty: standardized list and definitions of the Knee Society. Clin Orthop Relat Res 2013; 471: 215-20.
5. Losina E, Daigle ME, Suter LG, Hunter DJ, Solomon DH, Walensky RP, et al. Disease-modifying drugs for knee osteoarthritis: can they be cost-effective?. Osteoarthritis Cartilage 2013; 21: 655-67.
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7. Halpern B, Chaudhury S, Rodeo SA, Hayter C, Bogner E, Potter HG, et al. Clinical and MRI outcomes after platelet-rich plasma treatment for knee osteoarthritis. Clin J Sport Med 2013; 23: 238-9.
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9. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145-7.
10. Baschetti R. Ethics of embryonic stem cell technology: science versus philosophy. Intern Med J 2005; 35: 499-500; author reply 500-1.
11. Vats A, Tolley NS, Bishop AE, Polak JM. Embryonic stem cells and tissue engineering: delivering stem cells to the clinic. J R Soc Med 2005; 98: 346-50.
12. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-76.
13. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131: 861-72.
14. Gutierrez-Aranda I, Ramos-Mejia V, Bueno C, Munoz-Lopez M, Real PJ, Macia A, et al. Human induced pluripotent stem cells develop teratoma more efficiently and faster than human embryonic stem cells regardless the site of injection. Stem Cells 2010; 28: 1568-70.
15. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002; 13: 4279-95.
16. Noth U, Osyczka AM, Tuli R, Hickok NJ, Danielson KG, Tuan RS. Multilineage mesenchymal differentiation potential of human trabecular bone-derived cells. J Orthop Res 2002; 20: 1060-9.
17. Tuli R, Tuli S, Nandi S, Wang ML, Alexander PG, Haleem-Smith H, et al. Characterization of multipotential mesenchymal progenitor cells derived from human trabecular bone. Stem Cells 2003; 21: 681-93.
18. Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, et al. SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A 2003; 100: 5807-12.
19. Young HE, Steele TA, Bray RA, Hudson J, Floyd JA, Hawkins K, et al. Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec 2001; 264: 51-62.
20. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 2007; 25: 2739-49.
21. Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 1970; 3: 393-403.
22. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-7.
23. Caplan AI. Mesenchymal stem cells. J Orthop Res 1991; 9: 641-50.
24. Lennon DP, Caplan AI. Isolation of rat marrow-derived mesenchymal stem cells. Exp Hematol 2006; 34: 1606-7.
25. Nadri S, Soleimani M, Hosseni RH, Massumi M, Atashi A, Izadpanah R. An efficient method for isolation of murine bone marrow mesenchymal stem cells. Int J Dev Biol 2007; 51: 723-9.
26. Friedenstein AJ, Latzinik NV, Gorskaya Yu F, Luria EA, Moskvina IL. Bone marrow stromal colony formation requires stimulation by haemopoietic cells. Bone Miner 1992; 18: 199-213.
27. Latsinik NV, Gorskaia Iu F, Grosheva AG, Domogatskii SP, Kuznetsov SA. [The stromal colony-forming cell (CFUf) count in the bone marrow of mice and the clonal nature of the fibroblast colonies they form]. Ontogenez 1986; 17: 27-36.
28. McKinney-Freeman SL, Naveiras O, Yates F, Loewer S, Philitas M, Curran M, et al. Surface antigen phenotypes of hematopoietic stem cells from embryos and murine embryonic stem cells. Blood 2009; 114: 268-78.
29. Cros J, Cagnard N, Woollard K, Patey N, Zhang SY, Senechal B, et al. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 2010; 33: 375-86.
30. Nielsen JS, McNagny KM. Novel functions of the CD34 family. J Cell Sci 2008; 121: 3683-92.
31. Parant O, Dubernard G, Challier JC, Oster M, Uzan S, Aractingi S, et al. CD34+ cells in maternal placental blood are mainly fetal in origin and express endothelial markers. Lab Invest 2009; 89: 915-23.
32. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418: 41-9.
33. Simmons PJ, Torok-Storb B. Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood 1991; 78: 55-62.
34. Young HE, Steele TA, Bray RA, Detmer K, Blake LW, Lucas PW, et al. Human pluripotent and progenitor cells display cell surface cluster differentiation markers CD10, CD13, CD56, and MHC class-I. Proc Soc Exp Biol Med 1999; 221: 63-71.
35. Jones EA, Kinsey SE, English A, Jones RA, Straszynski L, Meredith DM, et al. Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells. Arthritis Rheum 2002; 46: 3349-60.
36. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-7.
37. Stenderup K, Justesen J, Eriksen EF, Rattan SI, Kassem M. Number and proliferative capacity of osteogenic stem cells are maintained during aging and in patients with osteoporosis. J Bone Miner Res 2001; 16: 1120-9.
38. Jorgensen NR, Henriksen Z, Sorensen OH, Civitelli R. Dexamethasone, BMP-2, and 1,25-dihydroxyvitamin D enhance a more differentiated osteoblast phenotype: validation of an in vitro model for human bone marrow-derived primary osteoblasts. Steroids 2004; 69: 219-26.
39. Heng BC, Cao T, Stanton LW, Robson P, Olsen B. Strategies for directing the differentiation of stem cells into the osteogenic lineage in vitro. J Bone Miner Res 2004; 19: 1379-94.
40. Yoo JU, Johnstone B. The role of osteochondral progenitor cells in fracture repair. Clin Orthop Relat Res 1998; (355 Suppl): S73-81.
41. Herlofsen SR, Kuchler AM, Melvik JE, Brinchmann JE. Chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells in self-gelling alginate discs reveals novel chondrogenic signature gene clusters. Tissue Eng Part A 2011; 17: 1003-13.
42. Pittenger MF. Mesenchymal stem cells from adult bone marrow. Methods Mol Biol 2008; 449: 27-44.
43. Rosen ED, Spiegelman BM. Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol 2000; 16: 145-71.
44. Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 2003; 48: 3464-74.
45. Al Faqeh H, Nor Hamdan BM, Chen HC, Aminuddin BS, Ruszymah BH. The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model. Exp Gerontol 2012; 47: 458-64.
46. Mokbel AN, El Tookhy OS, Shamaa AA, Rashed LA, Sabry D, El Sayed AM. Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model. BMC Musculoskelet Disord 2011; 12: 259.
47. ter Huurne M, Schelbergen R, Blattes R, Blom A, de Munter W, Grevers LC, et al. Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum 2012; 64: 3604-13.
48. Song F, Tang J, Geng R, Hu H, Zhu C, Cui W, et al. Comparison of the efficacy of bone marrow mononuclear cells and bone mesenchymal stem cells in the treatment of osteoarthritis in a sheep model. Int J Clin Exp Pathol 2014; 7: 1415-26.
49. Vilar JM, Morales M, Santana A, Spinella G, Rubio M, Cuervo B, et al. Controlled, blinded force platform analysis of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells associated to PRGF-Endoret in osteoarthritic dogs. BMC Vet Res 2013; 9: 131.
50. Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage 2002; 10: 199-206.
51. Wong KL, Lee KB, Tai BC, Law P, Lee EH, Hui JH. Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years' follow-up. Arthroscopy 2013; 29: 2020-8.
52. Saw KY, Hussin P, Loke SC, Azam M, Chen HC, Tay YG, et al. Articular cartilage regeneration with autologous marrow aspirate and hyaluronic Acid: an experimental study in a goat model. Arthroscopy 2009; 25: 1391-400.
53. Saw KY, Anz A, Merican S, Tay YG, Ragavanaidu K, Jee CS, et al. Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology. Arthroscopy 2011; 27: 493-506.
54. Saw KY, Anz A, Siew-Yoke Jee C, Merican S, Ching-Soong Ng R, Roohi SA, et al. Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial. Arthroscopy 2013; 29: 684-94.
55. Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, et al. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation 2013; 95: 1535-41.
56. Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, et al. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: two-year follow-up results. Transplantation 2014; 97: e66-8.
2. Dieppe PA, Lohmander LS. Pathogenesis and management of pain in osteoarthritis. Lancet 2005; 365: 965-73.
3. Katz JN. Total joint replacement in osteoarthritis. Best Pract Res Clin Rheumatol 2006; 20: 145-53.
4. Healy WL, Della Valle CJ, Iorio R, Berend KR, Cushner FD, Dalury DF, et al. Complications of total knee arthroplasty: standardized list and definitions of the Knee Society. Clin Orthop Relat Res 2013; 471: 215-20.
5. Losina E, Daigle ME, Suter LG, Hunter DJ, Solomon DH, Walensky RP, et al. Disease-modifying drugs for knee osteoarthritis: can they be cost-effective?. Osteoarthritis Cartilage 2013; 21: 655-67.
6. Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Regeneration of meniscus cartilage in a knee treated with percutaneously implanted autologous mesenchymal stem cells. Med Hypotheses 2008; 71: 900-8.
7. Halpern B, Chaudhury S, Rodeo SA, Hayter C, Bogner E, Potter HG, et al. Clinical and MRI outcomes after platelet-rich plasma treatment for knee osteoarthritis. Clin J Sport Med 2013; 23: 238-9.
8. Vangsness CT Jr, Farr J 2nd, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am 2014; 96: 90-8.
9. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145-7.
10. Baschetti R. Ethics of embryonic stem cell technology: science versus philosophy. Intern Med J 2005; 35: 499-500; author reply 500-1.
11. Vats A, Tolley NS, Bishop AE, Polak JM. Embryonic stem cells and tissue engineering: delivering stem cells to the clinic. J R Soc Med 2005; 98: 346-50.
12. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-76.
13. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131: 861-72.
14. Gutierrez-Aranda I, Ramos-Mejia V, Bueno C, Munoz-Lopez M, Real PJ, Macia A, et al. Human induced pluripotent stem cells develop teratoma more efficiently and faster than human embryonic stem cells regardless the site of injection. Stem Cells 2010; 28: 1568-70.
15. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002; 13: 4279-95.
16. Noth U, Osyczka AM, Tuli R, Hickok NJ, Danielson KG, Tuan RS. Multilineage mesenchymal differentiation potential of human trabecular bone-derived cells. J Orthop Res 2002; 20: 1060-9.
17. Tuli R, Tuli S, Nandi S, Wang ML, Alexander PG, Haleem-Smith H, et al. Characterization of multipotential mesenchymal progenitor cells derived from human trabecular bone. Stem Cells 2003; 21: 681-93.
18. Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, et al. SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A 2003; 100: 5807-12.
19. Young HE, Steele TA, Bray RA, Hudson J, Floyd JA, Hawkins K, et al. Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec 2001; 264: 51-62.
20. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 2007; 25: 2739-49.
21. Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 1970; 3: 393-403.
22. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-7.
23. Caplan AI. Mesenchymal stem cells. J Orthop Res 1991; 9: 641-50.
24. Lennon DP, Caplan AI. Isolation of rat marrow-derived mesenchymal stem cells. Exp Hematol 2006; 34: 1606-7.
25. Nadri S, Soleimani M, Hosseni RH, Massumi M, Atashi A, Izadpanah R. An efficient method for isolation of murine bone marrow mesenchymal stem cells. Int J Dev Biol 2007; 51: 723-9.
26. Friedenstein AJ, Latzinik NV, Gorskaya Yu F, Luria EA, Moskvina IL. Bone marrow stromal colony formation requires stimulation by haemopoietic cells. Bone Miner 1992; 18: 199-213.
27. Latsinik NV, Gorskaia Iu F, Grosheva AG, Domogatskii SP, Kuznetsov SA. [The stromal colony-forming cell (CFUf) count in the bone marrow of mice and the clonal nature of the fibroblast colonies they form]. Ontogenez 1986; 17: 27-36.
28. McKinney-Freeman SL, Naveiras O, Yates F, Loewer S, Philitas M, Curran M, et al. Surface antigen phenotypes of hematopoietic stem cells from embryos and murine embryonic stem cells. Blood 2009; 114: 268-78.
29. Cros J, Cagnard N, Woollard K, Patey N, Zhang SY, Senechal B, et al. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 2010; 33: 375-86.
30. Nielsen JS, McNagny KM. Novel functions of the CD34 family. J Cell Sci 2008; 121: 3683-92.
31. Parant O, Dubernard G, Challier JC, Oster M, Uzan S, Aractingi S, et al. CD34+ cells in maternal placental blood are mainly fetal in origin and express endothelial markers. Lab Invest 2009; 89: 915-23.
32. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418: 41-9.
33. Simmons PJ, Torok-Storb B. Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood 1991; 78: 55-62.
34. Young HE, Steele TA, Bray RA, Detmer K, Blake LW, Lucas PW, et al. Human pluripotent and progenitor cells display cell surface cluster differentiation markers CD10, CD13, CD56, and MHC class-I. Proc Soc Exp Biol Med 1999; 221: 63-71.
35. Jones EA, Kinsey SE, English A, Jones RA, Straszynski L, Meredith DM, et al. Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells. Arthritis Rheum 2002; 46: 3349-60.
36. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-7.
37. Stenderup K, Justesen J, Eriksen EF, Rattan SI, Kassem M. Number and proliferative capacity of osteogenic stem cells are maintained during aging and in patients with osteoporosis. J Bone Miner Res 2001; 16: 1120-9.
38. Jorgensen NR, Henriksen Z, Sorensen OH, Civitelli R. Dexamethasone, BMP-2, and 1,25-dihydroxyvitamin D enhance a more differentiated osteoblast phenotype: validation of an in vitro model for human bone marrow-derived primary osteoblasts. Steroids 2004; 69: 219-26.
39. Heng BC, Cao T, Stanton LW, Robson P, Olsen B. Strategies for directing the differentiation of stem cells into the osteogenic lineage in vitro. J Bone Miner Res 2004; 19: 1379-94.
40. Yoo JU, Johnstone B. The role of osteochondral progenitor cells in fracture repair. Clin Orthop Relat Res 1998; (355 Suppl): S73-81.
41. Herlofsen SR, Kuchler AM, Melvik JE, Brinchmann JE. Chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells in self-gelling alginate discs reveals novel chondrogenic signature gene clusters. Tissue Eng Part A 2011; 17: 1003-13.
42. Pittenger MF. Mesenchymal stem cells from adult bone marrow. Methods Mol Biol 2008; 449: 27-44.
43. Rosen ED, Spiegelman BM. Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol 2000; 16: 145-71.
44. Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 2003; 48: 3464-74.
45. Al Faqeh H, Nor Hamdan BM, Chen HC, Aminuddin BS, Ruszymah BH. The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model. Exp Gerontol 2012; 47: 458-64.
46. Mokbel AN, El Tookhy OS, Shamaa AA, Rashed LA, Sabry D, El Sayed AM. Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model. BMC Musculoskelet Disord 2011; 12: 259.
47. ter Huurne M, Schelbergen R, Blattes R, Blom A, de Munter W, Grevers LC, et al. Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum 2012; 64: 3604-13.
48. Song F, Tang J, Geng R, Hu H, Zhu C, Cui W, et al. Comparison of the efficacy of bone marrow mononuclear cells and bone mesenchymal stem cells in the treatment of osteoarthritis in a sheep model. Int J Clin Exp Pathol 2014; 7: 1415-26.
49. Vilar JM, Morales M, Santana A, Spinella G, Rubio M, Cuervo B, et al. Controlled, blinded force platform analysis of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells associated to PRGF-Endoret in osteoarthritic dogs. BMC Vet Res 2013; 9: 131.
50. Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Osteoarthritis Cartilage 2002; 10: 199-206.
51. Wong KL, Lee KB, Tai BC, Law P, Lee EH, Hui JH. Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years' follow-up. Arthroscopy 2013; 29: 2020-8.
52. Saw KY, Hussin P, Loke SC, Azam M, Chen HC, Tay YG, et al. Articular cartilage regeneration with autologous marrow aspirate and hyaluronic Acid: an experimental study in a goat model. Arthroscopy 2009; 25: 1391-400.
53. Saw KY, Anz A, Merican S, Tay YG, Ragavanaidu K, Jee CS, et al. Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology. Arthroscopy 2011; 27: 493-506.
54. Saw KY, Anz A, Siew-Yoke Jee C, Merican S, Ching-Soong Ng R, Roohi SA, et al. Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial. Arthroscopy 2013; 29: 684-94.
55. Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, et al. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation 2013; 95: 1535-41.
56. Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, et al. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: two-year follow-up results. Transplantation 2014; 97: e66-8.