Allogenic Mesenchymal Stem Cell for Bone Defect or Non Union Fracture

Summary

Mesenchymal stem cell (MSC) is one kind of stem cell which is gained form adult tissue. Although MSC derived from autogenic bone marrow are proven to help regeneration in non union fracture and long bone defect, the aspiration process through iliac crest is invasive and painful. Therefore, alternative source of MSC which is less invasive is needed. Adipose and umbilical cord is a "waste product" that proven to contain enormous MSC. Furthermore adipose and umbilical cord as an allogenic source is more abundant in number compares to autogenic bone marrow. This enormous source need and adequate preservation technique before applied to the patient. According to that, researchers want to explore the potency of MSC from bone marrow, umbilical cord and adipose as the source of allogenic MSC and the effect of cryopreservation technique to the viability and quality of MSC. We will also compare the effectivity of MSC implantation from bone marrow, umbilical cord and adipose applied to non union fracture and long bone defect. Samples from bone marrow, umbilical cord and adipose are cultured and the viability of the cells are observed. Some of the cells are implanted directly to the patient with non union fractures and long bone defect while some are cryopreserved in liquid nitrogen -190 degree Celsius in three months. All samples are thawed and the viability of the cells are observed. Patient who are implanted by MSC allogenic will undergo clinical and radiological examination in the third, sixth and twenty second month after implantation.

Timeline

Start

2014-08

Primary completion

2017-12

Completion

2017-12

Publications

• Background Kon E, Muraglia A, Corsi A, Bianco P, Marcacci M, Martin I, Boyde A, Ruspantini I, Chistolini P, Rocca M, Giardino R, Cancedda R, Quarto R. Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. J Biomed Mater Res. 2000 Mar 5;49(3):328-37. doi: 10.1002/(sici)1097-4636(20000305)49:33.0.co;2-q.
• Background Hee HT, Ismail HD, Lim CT, Goh JC, Wong HK. Effects of implantation of bone marrow mesenchymal stem cells, disc distraction and combined therapy on reversing degeneration of the intervertebral disc. J Bone Joint Surg Br. 2010 May;92(5):726-36. doi: 10.1302/0301-620X.92B5.23015.
• Background Ye Z, Wang Y, Xie HY, Zheng SS. Immunosuppressive effects of rat mesenchymal stem cells: involvement of CD4+CD25+ regulatory T cells. Hepatobiliary Pancreat Dis Int. 2008 Dec;7(6):608-14.
• Background Bocelli-Tyndall C, Bracci L, Spagnoli G, Braccini A, Bouchenaki M, Ceredig R, Pistoia V, Martin I, Tyndall A. Bone marrow mesenchymal stromal cells (BM-MSCs) from healthy donors and auto-immune disease patients reduce the proliferation of autologous- and allogeneic-stimulated lymphocytes in vitro. Rheumatology (Oxford). 2007 Mar;46(3):403-8. doi: 10.1093/rheumatology/kel267. Epub 2006 Aug 18.
• Background Yanez R, Lamana ML, Garcia-Castro J, Colmenero I, Ramirez M, Bueren JA. Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem Cells. 2006 Nov;24(11):2582-91. doi: 10.1634/stemcells.2006-0228. Epub 2006 Jul 27.
• Background Tipnis S, Viswanathan C, Majumdar AS. Immunosuppressive properties of human umbilical cord-derived mesenchymal stem cells: role of B7-H1 and IDO. Immunol Cell Biol. 2010 Nov-Dec;88(8):795-806. doi: 10.1038/icb.2010.47. Epub 2010 Apr 13.
• Results Hou ZL, Liu Y, Mao XH, Wei CY, Meng MY, Liu YH, Zhuyun Yang Z, Zhu H, Short M, Bernard C, Xiao ZC. Transplantation of umbilical cord and bone marrow-derived mesenchymal stem cells in a patient with relapsing-remitting multiple sclerosis. Cell Adh Migr. 2013 Sep-Oct;7(5):404-7. doi: 10.4161/cam.26941. Epub 2013 Oct 30.
• Results Brinker MR, O'Connor DP. The incidence of fractures and dislocations referred for orthopaedic services in a capitated population. J Bone Joint Surg Am. 2004 Feb;86(2):290-7.
• Results Liebergall M, Schroeder J, Mosheiff R, Gazit Z, Yoram Z, Rasooly L, Daskal A, Khoury A, Weil Y, Beyth S. Stem cell-based therapy for prevention of delayed fracture union: a randomized and prospective preliminary study. Mol Ther. 2013 Aug;21(8):1631-8. doi: 10.1038/mt.2013.109. Epub 2013 Jun 4.
• Results Sen MK, Miclau T. Autologous iliac crest bone graft: should it still be the gold standard for treating nonunions? Injury. 2007 Mar;38 Suppl 1:S75-80. doi: 10.1016/j.injury.2007.02.012.
• Results Goulet JA, Senunas LE, DeSilva GL, Greenfield ML. Autogenous iliac crest bone graft. Complications and functional assessment. Clin Orthop Relat Res. 1997 Jun;(339):76-81. doi: 10.1097/00003086-199706000-00011.
• Results Mauney JR, Volloch V, Kaplan DL. Role of adult mesenchymal stem cells in bone tissue engineering applications: current status and future prospects. Tissue Eng. 2005 May-Jun;11(5-6):787-802. doi: 10.1089/ten.2005.11.787.
• Results Cavallo C, Cuomo C, Fantini S, Ricci F, Tazzari PL, Lucarelli E, Donati D, Facchini A, Lisignoli G, Fornasari PM, Grigolo B, Moroni L. Comparison of alternative mesenchymal stem cell sources for cell banking and musculoskeletal advanced therapies. J Cell Biochem. 2011 May;112(5):1418-30. doi: 10.1002/jcb.23058.
• Results Jurgens WJ, Oedayrajsingh-Varma MJ, Helder MN, Zandiehdoulabi B, Schouten TE, Kuik DJ, Ritt MJ, van Milligen FJ. Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies. Cell Tissue Res. 2008 Jun;332(3):415-26. doi: 10.1007/s00441-007-0555-7. Epub 2008 Apr 1.
• Results Lu Z, Wang G, Dunstan CR, Chen Y, Lu WY, Davies B, Zreiqat H. Activation and promotion of adipose stem cells by tumour necrosis factor-alpha preconditioning for bone regeneration. J Cell Physiol. 2013 Aug;228(8):1737-44. doi: 10.1002/jcp.24330.
• Results Parolini O, Alviano F, Bagnara GP, Bilic G, Buhring HJ, Evangelista M, Hennerbichler S, Liu B, Magatti M, Mao N, Miki T, Marongiu F, Nakajima H, Nikaido T, Portmann-Lanz CB, Sankar V, Soncini M, Stadler G, Surbek D, Takahashi TA, Redl H, Sakuragawa N, Wolbank S, Zeisberger S, Zisch A, Strom SC. Concise review: isolation and characterization of cells from human term placenta: outcome of the first international Workshop on Placenta Derived Stem Cells. Stem Cells. 2008 Feb;26(2):300-11. doi: 10.1634/stemcells.2007-0594. Epub 2007 Nov 1.
• Results Troyer DL, Weiss ML. Wharton's jelly-derived cells are a primitive stromal cell population. Stem Cells. 2008 Mar;26(3):591-9. doi: 10.1634/stemcells.2007-0439. Epub 2007 Dec 6.
• Results Bernardo ME, Emons JA, Karperien M, Nauta AJ, Willemze R, Roelofs H, Romeo S, Marchini A, Rappold GA, Vukicevic S, Locatelli F, Fibbe WE. Human mesenchymal stem cells derived from bone marrow display a better chondrogenic differentiation compared with other sources. Connect Tissue Res. 2007;48(3):132-40. doi: 10.1080/03008200701228464.
• Results Im GI, Shin YW, Lee KB. Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? Osteoarthritis Cartilage. 2005 Oct;13(10):845-53. doi: 10.1016/j.joca.2005.05.005.
• Results Jin HJ, Bae YK, Kim M, Kwon SJ, Jeon HB, Choi SJ, Kim SW, Yang YS, Oh W, Chang JW. Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. Int J Mol Sci. 2013 Sep 3;14(9):17986-8001. doi: 10.3390/ijms140917986.
• Results Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006 May;24(5):1294-301. doi: 10.1634/stemcells.2005-0342. Epub 2006 Jan 12.
• Results Miao Z, Jin J, Chen L, Zhu J, Huang W, Zhao J, Qian H, Zhang X. Isolation of mesenchymal stem cells from human placenta: comparison with human bone marrow mesenchymal stem cells. Cell Biol Int. 2006 Sep;30(9):681-7. doi: 10.1016/j.cellbi.2006.03.009. Epub 2006 Apr 22.
• Results Hu L, Hu J, Zhao J, Liu J, Ouyang W, Yang C, Gong N, Du L, Khanal A, Chen L. Side-by-side comparison of the biological characteristics of human umbilical cord and adipose tissue-derived mesenchymal stem cells. Biomed Res Int. 2013;2013:438243. doi: 10.1155/2013/438243. Epub 2013 Jul 7.
• Results Toupadakis CA, Wong A, Genetos DC, Cheung WK, Borjesson DL, Ferraro GL, Galuppo LD, Leach JK, Owens SD, Yellowley CE. Comparison of the osteogenic potential of equine mesenchymal stem cells from bone marrow, adipose tissue, umbilical cord blood, and umbilical cord tissue. Am J Vet Res. 2010 Oct;71(10):1237-45. doi: 10.2460/ajvr.71.10.1237.
• Results Shafiee A, Seyedjafari E, Soleimani M, Ahmadbeigi N, Dinarvand P, Ghaemi N. A comparison between osteogenic differentiation of human unrestricted somatic stem cells and mesenchymal stem cells from bone marrow and adipose tissue. Biotechnol Lett. 2011 Jun;33(6):1257-64. doi: 10.1007/s10529-011-0541-8. Epub 2011 Feb 2.
• Results Arinzeh TL, Peter SJ, Archambault MP, van den Bos C, Gordon S, Kraus K, Smith A, Kadiyala S. Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg Am. 2003 Oct;85(10):1927-35. doi: 10.2106/00004623-200310000-00010.
• Results Bruder SP, Kraus KH, Goldberg VM, Kadiyala S. The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. J Bone Joint Surg Am. 1998 Jul;80(7):985-96. doi: 10.2106/00004623-199807000-00007.
• Results Viateau V, Guillemin G, Bousson V, Oudina K, Hannouche D, Sedel L, Logeart-Avramoglou D, Petite H. Long-bone critical-size defects treated with tissue-engineered grafts: a study on sheep. J Orthop Res. 2007 Jun;25(6):741-9. doi: 10.1002/jor.20352.
• Results Schubert T, Lafont S, Beaurin G, Grisay G, Behets C, Gianello P, Dufrane D. Critical size bone defect reconstruction by an autologous 3D osteogenic-like tissue derived from differentiated adipose MSCs. Biomaterials. 2013 Jun;34(18):4428-38. doi: 10.1016/j.biomaterials.2013.02.053. Epub 2013 Mar 16.
• Results Shoji T, Ii M, Mifune Y, Matsumoto T, Kawamoto A, Kwon SM, Kuroda T, Kuroda R, Kurosaka M, Asahara T. Local transplantation of human multipotent adipose-derived stem cells accelerates fracture healing via enhanced osteogenesis and angiogenesis. Lab Invest. 2010 Apr;90(4):637-49. doi: 10.1038/labinvest.2010.39. Epub 2010 Feb 15.
• Results Thirumala S, Goebel WS, Woods EJ. Clinical grade adult stem cell banking. Organogenesis. 2009 Jul;5(3):143-54. doi: 10.4161/org.5.3.9811.
• Results Matsumura K, Hayashi F, Nagashima T, Hyon SH. Long-term cryopreservation of human mesenchymal stem cells using carboxylated poly-l-lysine without the addition of proteins or dimethyl sulfoxide. J Biomater Sci Polym Ed. 2013;24(12):1484-97. doi: 10.1080/09205063.2013.771318. Epub 2013 Feb 22.
• Results Dariolli R, Bassaneze V, Nakamuta JS, Omae SV, Campos LC, Krieger JE. Porcine adipose tissue-derived mesenchymal stem cells retain their proliferative characteristics, senescence, karyotype and plasticity after long-term cryopreservation. PLoS One. 2013 Jul 9;8(7):e67939. doi: 10.1371/journal.pone.0067939. Print 2013.
• Results Angelo PC, Ferreira AC, Fonseca VD, Frade SP, Ferreira CS, Malta FS, Pereira AK, Leite HV, Brum AP, Pardini VC, Gomes KB, Cabral AC. Cryopreservation does not alter karyotype, multipotency, or NANOG/SOX2 gene expression of amniotic fluid mesenchymal stem cells. Genet Mol Res. 2012 Apr 19;11(2):1002-12. doi: 10.4238/2012.April.19.5.
• Results Park M, Seo JJ. Role of HLA in Hematopoietic Stem Cell Transplantation. Bone Marrow Res. 2012;2012:680841. doi: 10.1155/2012/680841. Epub 2012 Oct 2.
• Results Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999 Apr 2;284(5411):143-7. doi: 10.1126/science.284.5411.143.
• Results Liu LY, Chai JK, Duan HJ, Hou YS, Yin HN, Yu YH, Hu Q, Hao DF, Feng G, Li T, Du JD. [Comparison of different methods for the isolation of human umbilical cord mesenchymal stem cells]. Zhonghua Yi Xue Za Zhi. 2013 Aug 27;93(32):2592-6. Chinese.
• Results Han ZX, Shi Q, Wang DK, Li D, Lyu M. [Basic biological characteristics of mesenchymal stem cells derived from bone marrow and human umbilical cord]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Oct;21(5):1248-55. doi: 10.7534/j.issn.1009-2137.2013.05.033. Chinese.

Drugs

Indications

No indication recorded.