Clin Orthop Surg.  2016 Mar;8(1):1-8. 10.4055/cios.2016.8.1.1.

Stem Cell Therapy for the Treatment of Hip Osteonecrosis: A 30-Year Review of Progress

• Hernigou P
• Trousselier M
• Roubineau
• Bouthors C
• Chevallier N
• Rouard H
• Flouzat-Lachaniette CH

• KMID: 2363939
• DOI: http://doi.org/10.4055/cios.2016.8.1.1

Abstract

Avascular necrosis of the femoral head is caused by a multitude of etiologic factors and is associated with collapse with a risk of hip arthroplasty in younger populations. A focus on early disease management with the use of stem cells was proposed as early as 1985 by the senior author (PH). We undertook a systematic review of the medical literature to examine the progress in cell therapy during the last 30 years for the treatment of early stage osteonecrosis.

Keyword

Hip; Osteonecrosis; Cell therapy; Mesenchymal stromal cells; Tissue engineering

MeSH Terms

*Cell- and Tissue-Based Therapy
Femur Head/*surgery
Femur Head Necrosis/*surgery
Humans
*Mesenchymal Stem Cell Transplantation
*Tissue Engineering

Reference

1. Hernigou P, Beaujean F. La moelle osseuse, une cle dans la comprehension des necroses de hanche idiopathiques. Rev Rhum Mal Osteoartic. 1993; 60(10):722.

2. Hernigou P, Beaujean F. Bone marrow activity in the upper femoral extremity in avascular osteonecrosis. Rev Rhum Engl Ed. 1993; 60(1):610.

3. Hernigou P, Beaujean F. Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res. 2002; (405):14–23.

4. Hernigou P, Beaujean F. Abnormalities in the bone marrow of the iliac crest in patients who have osteonecrosis secondary to corticosteroid therapy or alcohol abuse. J Bone Joint Surg Am. 1997; 79(7):1047–1053.

5. Hernigou P, Beaujean F, Lambotte JC. Decrease in the mesenchymal stem-cell pool in the proximal femur in corticosteroid-induced osteonecrosis. J Bone Joint Surg Br. 1999; 81(2):349–355.

6. Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol. 1966; 16(3):381–390.

7. Bianco P, Riminucci M, Gronthos S, Robey PG. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells. 2001; 19(3):180–192.

8. Conway EM, Collen D, Carmeliet P. Molecular mechanisms of blood vessel growth. Cardiovasc Res. 2001; 49(3):507–521.

9. Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013; 45:e54.

10. Hernigou P. Bone transplantation and tissue engineering, part IV. Mesenchymal stem cells: history in orthopedic surgery from Cohnheim and Goujon to the Nobel Prize of Yamanaka. Int Orthop. 2015; 39(4):807–817.

11. Hernigou P, Manicom O, Poignard A, Nogier A, Filippini P, De Abreu L. Core decompression with marrow stem cells. Oper Tech Orthop. 2004; 14(2):68–74.

12. Hernigou P, Zilber S, Filippini P, Rouard H, Mathieu G, Poignard A. Bone marrow injection in hip osteonecrosis. Tech Orthop. 2008; 23(1):18–25.

13. Hernigou P, Homma Y, Flouzat Lachaniette CH, et al. Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells. Int Orthop. 2013; 37(11):2279–2287.

14. Hernigou J, Picard L, Alves A, Silvera J, Homma Y, Hernigou P. Understanding bone safety zones during bone marrow aspiration from the iliac crest: the sector rule. Int Orthop. 2014; 38(11):2377–2384.

15. Hernigou J, Alves A, Homma Y, Guissou I, Hernigou P. Anatomy of the ilium for bone marrow aspiration: map of sectors and implication for safe trocar placement. Int Orthop. 2014; 38(12):2585–2590.

16. Hernigou P, Poignard A, Zilber S, Rouard H. Cell therapy of hip osteonecrosis with autologous bone marrow grafting. Indian J Orthop. 2009; 43(1):40–45.

17. Gangji V, Hauzeur JP, Matos C, De Maertelaer V, Toungouz M, Lambermont M. Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells: a pilot study. J Bone Joint Surg Am. 2004; 86(6):1153–1160.

18. Gangji V, De Maertelaer V, Hauzeur JP. Autologous bone marrow cell implantation in the treatment of non-traumatic osteonecrosis of the femoral head: five year follow-up of a prospective controlled study. Bone. 2011; 49(5):1005–1009.

19. Papakostidis C, Tosounidis TH, Jones E, Giannoudis PV. The role of "cell therapy" in osteonecrosis of the femoral head. Acta Orthop. 2016; 87(1):72–78.

20. Hernigou P, Flouzat-Lachaniette CH, Delambre J, et al. Osteonecrosis repair with bone marrow cell therapies: state of the clinical art. Bone. 2015; 70:102–109.

21. Kawate K, Yajima H, Ohgushi H, et al. Tissue-engineered approach for the treatment of steroid-induced osteonecrosis of the femoral head: transplantation of autologous mesenchymal stem cells cultured with beta-tricalcium phosphate ceramics and free vascularized fibula. Artif Organs. 2006; 30(12):960–962.

22. Kang JS, Moon KH, Park SR, Kang SB, Park HB, Lee SH. Clinical results of autoiliac cancellous bone graft combined with implantation of autologous bone marrow cells for osteonecrosis of the femoral head. J Korean Orthop Assoc. 2008; 43(1):1–8.

23. Liu L, Sun Z, Chen B, et al. Ex vivo expansion and in vivo infusion of bone marrow-derived Flk-1+CD31-CD34- mesenchymal stem cells: feasibility and safety from monkey to human. Stem Cells Dev. 2006; 15(3):349–357.

24. Yan Z, Hang D, Guo C, Chen Z. Fate of mesenchymal stem cells transplanted to osteonecrosis of femoral head. J Orthop Res. 2009; 27(4):442–446.

25. Yamasaki T, Yasunaga Y, Ishikawa M, Hamaki T, Ochi M. Bone-marrow-derived mononuclear cells with a porous hydroxyapatite scaffold for the treatment of osteonecrosis of the femoral head: a preliminary study. J Bone Joint Surg Br. 2010; 92(3):337–341.

26. Wang BL, Sun W, Shi ZC, et al. Treatment of nontraumatic osteonecrosis of the femoral head with the implantation of core decompression and concentrated autologous bone marrow containing mononuclear cells. Arch Orthop Trauma Surg. 2010; 130(7):859–865.

27. Rackwitz L, Eden L, Reppenhagen S, et al. Stem cell- and growth factor-based regenerative therapies for avascular necrosis of the femoral head. Stem Cell Res Ther. 2012; 3(1):7.

28. Zhao D, Cui D, Wang B, et al. Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells. Bone. 2012; 50(1):325–330.

29. Liu Y, Liu S, Su X. Core decompression and implantation of bone marrow mononuclear cells with porous hydroxylapatite composite filler for the treatment of osteonecrosis of the femoral head. Arch Orthop Trauma Surg. 2013; 133(1):125–133.

30. Mao Q, Jin H, Liao F, Xiao L, Chen D, Tong P. The efficacy of targeted intraarterial delivery of concentrated autologous bone marrow containing mononuclear cells in the treatment of osteonecrosis of the femoral head: a five year follow-up study. Bone. 2013; 57(2):509–516.

31. Hernigou P, Lambotte JC. Volumetric analysis of osteonecrosis of the femur: anatomical correlation using MRI. J Bone Joint Surg Br. 2001; 83(5):672–675.

32. Hernigou P, Lambotte JC. Bilateral hip osteonecrosis: influence of hip size on outcome. Ann Rheum Dis. 2000; 59(10):817–821.

33. Homma Y, Kaneko K, Hernigou P. Supercharging allografts with mesenchymal stem cells in the operating room during hip revision. Int Orthop. 2014; 38(10):2033–2044.

34. Parfitt AM, Drezner MK, Glorieux FH, et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 1987; 2(6):595–610.

35. Frost HM. Intermediary organization of the skeleton. Boca Raton: CRC Press;1986.

36. Jones EA, Yang XB. Mesenchymal stem cells and their future in bone repair. Int J Adv Rheumatol. 2005; 3(3):15–21.

37. Gangji V, Hauzeur JP. Cellular-based therapy for osteonecrosis. Orthop Clin North Am. 2009; 40(2):213–221.

38. Poignard A, Lebouvier A, Cavet M, et al. New preclinical porcine model of femoral head osteonecrosis to test mesenchymal stromal cell efficiency in regenerative medicine. Int Orthop. 2014; 38(9):1837–1844.

39. Leotot J, Lebouvier A, Hernigou P, Bierling P, Rouard H, Chevallier N. Bone-forming capacity and biodistribution of bone marrow-derived stromal cells directly loaded into scaffolds: a novel and easy approach for clinical application of bone regeneration. Cell Transplant. 2015; 24(10):1945–1955.

40. Lebouvier A, Poignard A, Cavet M, et al. Development of a simple procedure for the treatment of femoral head osteonecrosis with intra-osseous injection of bone marrow mesenchymal stromal cells: study of their biodistribution in the early time points after injection. Stem Cell Res Ther. 2015; 6:68.

41. Lebouvier A, Poignard A, Coquelin-Salsac L, et al. Autologous bone marrow stromal cells are promising candidates for cell therapy approaches to treat bone degeneration in sickle cell disease. Stem Cell Res. 2015; 15(3):584–594.

42. Hernigou P, Bernaudin F, Reinert P, Kuentz M, Vernant JP. Bone-marrow transplantation in sickle-cell disease. Effect on osteonecrosis: a case report with a four-year follow-up. J Bone Joint Surg Am. 1997; 79(11):1726–1730.

43. Xiao ZM, Jiang H, Zhan XL, Wu ZG, Zhang XL. Treatment of osteonecrosis of femoral head with BMSCs-seeded bioderived bone materials combined with rhBMP-2 in rabbits. Chin J Traumatol. 2008; 11(3):165–170.

44. Tang TT, Lu B, Yue B, et al. Treatment of osteonecrosis of the femoral head with hBMP-2-gene-modified tissue-engineered bone in goats. J Bone Joint Surg Br. 2007; 89(1):127–129.

45. Wen Q, Ma L, Chen YP, Yang L, Luo W, Wang XN. Treatment of avascular necrosis of the femoral head by hepatocyte growth factor-transgenic bone marrow stromal stem cells. Gene Ther. 2008; 15(23):1523–1535.

46. Hernigou P, Homma Y, Flouzat-Lachaniette CH, Poignard A, Chevallier N, Rouard H. Cancer risk is not increased in patients treated for orthopaedic diseases with autologous bone marrow cell concentrate. J Bone Joint Surg Am. 2013; 95(24):2215–2221.

47. Hernigou P, Flouzat Lachaniette CH, Delambre J, Chevallier N, Rouard H. Regenerative therapy with mesenchymal stem cells at the site of malignant primary bone tumour resection: what are the risks of early or late local recurrence? Int Orthop. 2014; 38(9):1825–1835.