Abstract
For developing a clinically effective bone regeneration strategy, we compare the bone regeneration potential of cultured allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) and of autologous BM-MSCs loaded onto allogeneic cancellous bone granule scaffolds. A critical-sized segmental bone defect was made at the mid-shaft of both radiuses in 19 New Zealand White rabbits (NWRs). In the experimental group, allogeneic BM-MSCs loaded onto small-sized allogeneic cancellous bone granules (300~700 um in diameter) were implanted in one side of a bone defect. In the control group, autologous BM-MSCs loaded onto allogeneic cancellous granules were grafted in the other side. Bone regeneration was assessed by radiographic evaluation at 4, 8, 12 and 16 weeks post-implantation and by micro-computed tomography (micro-CT) and histological evaluation at 8 and 16 weeks. The experimental groups showed lower bone quantity indices (BQIs) than the control groups at 12 and 16 weeks (p < 0.05), although no significant difference was observed at 4 and 8 weeks (p > 0.05). Micro-CT analysis revealed that both groups had similar mean total bone volume and other parameters including trabecular thickness, number and separation at either 8 or 16 weeks. Only bone surface area revealed less area in the experimental group at 16 weeks. Histological evaluation of 8-week and 16-week specimens showed similar biologic processes of new bone formation and maturation. There was no inflammatory reaction indicating an adverse immune response in both allogeneic and autologous MSC groups. In conclusion, allogeneic BM-MSCs loaded onto allogeneic cancellous bone granules had comparable bone regeneration potential to autologous BM-MSCs in a rabbit radial defect model.
References
Aho AJ, Ekfors T, Dean PB, Aro HT, Ahonen A and Nikkanen V (1994) Incorporation and clinical results of large allografts of the extremities and pelvis. Clin Orthop Relat Res 200–213
Arinzeh TL, Peter SJ, Archambault MP, van den Bos C, Gordon S, Kraus K, Smith A, Kadiyala S (2003) Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg Am 85-A:1927–1935
Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30:42–48
Bruder SP, Kraus KH, Goldberg VM, Kadiyala S (1998) The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. J Bone Joint Surg Am 80:985–996
Chao PH, Grayson W, Vunjak-Novakovic G (2007) Engineering cartilage and bone using human mesenchymal stem cells. J Orthop Sci 12:398–404
Coathup MJ, Kalia P, Konan S, Mirza K, Blunn GW (2013) A comparison of allogeneic and autologous mesenchymal stromal cells and osteoprogenitor cells in augmenting bone formation around massive bone tumor prostheses. J Biomed Mater Res A 101:2210–2218
Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99:3838–3843
Ehrler DM, Vaccaro AR (2000) The use of allograft bone in lumbar spine surgery. Clin Orthop Relat Res 371:38–45
Eliopoulos N, Stagg J, Lejeune L, Pommey S, Galipeau J (2005) Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice. Blood 106:4057–4065
Gazdag AR, Lane JM, Glaser D, Forster RA (1995) Alternatives to Autogenous Bone Graft: Efficacy and Indications. J Am Acad Orthop Surg 3:1–8
Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP (1997) Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem 64:295–312
Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU (1998) In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 238:265–272
Kadiyala S, Young RG, Thiede MA, Bruder SP (1997) Culture expanded canine mesenchymal stem cells possess osteochondrogenic potential in vivo and in vitro. Cell Transplant 6:125–134
Kim SJ, Chung YG, Lee YK, Oh IW, Kim YS, Moon YS (2012) Comparison of the osteogenic potentials of autologous cultured osteoblasts and mesenchymal stem cells loaded onto allogeneic cancellous bone granules. Cell Tissue Res 347:303–310
Lee SU, Chung YG, Oh IH, Kim JM, Kim YS, Lee YG, Baek MH, Kim SE (2010) Bone regeneration using mesenchymal stem cells loaded onto allogeneic cancellous bone granules. Tissue Eng Regen Med 7:401–409
Li ZH, Liao W, Cui XL, Zhao Q, Liu M, Chen YH, Liu TS, Liu NL, Wang F, Yi Y, Shao NS (2011) Intravenous transplantation of allogeneic bone marrow mesenchymal stem cells and its directional migration to the necrotic femoral head. Int J Med Sci 8:74–83
Lucarelli E, Donati D, Cenacchi A, Fornasari PM (2004) Bone reconstruction of large defects using bone marrow derived autologous stem cells. Transfus Apher Sci 30:169–174
Mackay AM, Beck SC, Murphy JM, Barry FP, Chichester CO, Pittenger MF (1998) Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow. Tissue Eng 4:415–428
Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2:595–610
Patel SA, Sherman L, Munoz J, Rameshwar P (2008) Immunological properties of mesenchymal stem cells and clinical implications. Arch Immunol Ther Exp (Warsz) 56:1–8
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147
Planka L, Gal P, Kecova H, Klima J, Hlucilova J, Filova E, Amler E, Krupa P, Kren L, Srnec R, Urbanova L, Lorenzova J, Necas A (2008) Allogeneic and autogenous transplantations of MSCs in treatment of the physeal bone bridge in rabbits. BMC Biotechnol 8:70
Poncelet AJ, Vercruysse J, Saliez A, Gianello P (2007) Although pig allogeneic mesenchymal stem cells are not immunogenic in vitro, intracardiac injection elicits an immune response in vivo. Transplantation 83:783–790
Pruss A, Perka C, Degenhardt P, Maronna U, Buttner-Janz K, Paul B, Muller K, Klumpp C, Bruck JC, Von Versen R (2002) Clinical efficacy and compatibility of allogeneic avital tissue transplants sterilized with a peracetic acid/ethanol mixture. Cell Tissue Bank 3:235–243
Quarto R, Mastrogiacomo M, Cancedda R, Kutepov SM, Mukhachev V, Lavroukov A, Kon E, Marcacci M (2001) Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med 344:385–386
Seebach C, Schultheiss J, Wilhelm K, Frank J, Henrich D (2010) Comparison of six bone-graft substitutes regarding to cell seeding efficiency, metabolism and growth behaviour of human mesenchymal stem cells (MSC) in vitro. Injury 41:731–738
Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T (2002) Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 360:427–435
Udehiya RK, Amarpal AHP, Kinjavdekar P, Pawde AM, Singh R, Taru Sharma G (2013) Comparison of autogenic and allogenic bone marrow derived mesenchymal stem cells for repair of segmental bone defects in rabbits. Res Vet Sci 94:743–752
Younger EM, Chapman MW (1989) Morbidity at bone graft donor sites. J Orthop Trauma 3:192–195
Zomorodian E, Baghaban Eslaminejad M (2012) Mesenchymal stem cells as a potent cell source for bone regeneration. Stem Cells Int. doi:10.1155/2012/980353
Acknowledgments
The authors wish to express their gratitude to the department of radiology for their help in radiographic evaluations. We also thank Je-Sun Chang for his help in micro-CT image analysis. Fundings for this study were kindly provided by Seoul St. Mary’s Clinical Medicine Research Program of year 2012 through the Catholic University of Korea and Il-dong Pharmaceutical Co., Ltd., Seoul, Korea.
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The authors declare that they have no competing interests.
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Kang, SH., Chung, YG., Oh, IH. et al. Bone regeneration potential of allogeneic or autogeneic mesenchymal stem cells loaded onto cancellous bone granules in a rabbit radial defect model. Cell Tissue Res 355, 81–88 (2014). https://doi.org/10.1007/s00441-013-1738-z
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DOI: https://doi.org/10.1007/s00441-013-1738-z