SCD  Vol.2 No.1 , January 2012
Characterization of a mesenchymal stem cell line that differentiates to bone and provides niches supporting mouse and human hematopoietic stem cells
ABSTRACT
Identification of mouse cell lines with properties of primary multipotential mesenchymal stromal cells (MSC) is required to facilitate the use of mouse models for evaluation of mechanisms in bone formation, hematopoiesis and cellular therapies for regenerative medicine. Primary murine MSC vary between strains, are difficult to grow in vitro and have inconsistent properties. The main aim of the study was to establish OMA-AD cells as an appropriate model system to conduct studies on MSC, bone formation and hematopoiesis. OMA-AD cells were isolated by differential trypsinization of C57BL/6J mouse bone marrow (BM) cells. The cells were then repassaged, cloned and characterized. OMA-AD cells were immortal and non-tumorigenic, differentiated readily to all mesenchymal cell types including bone, supported mouse and human hematopoiesis and were immunosuppressive. Our results demonstrated that OMA-AD cells possessed the properties of primary MSC. In addition, these cells grew readily and consistently, thereby facilitating future studies of bone formation, hematopoiesis and mesenchymal cells for regenerative medicine.

Cite this paper
Tuljapurkar, S. , Jackson, J. , Brusnahan, S. , O’Kane, B. and Sharp, J. (2012) Characterization of a mesenchymal stem cell line that differentiates to bone and provides niches supporting mouse and human hematopoietic stem cells. Stem Cell Discovery, 2, 5-14. doi: 10.4236/scd.2012.21002.
References
[1]   Zhang, J., Niu, C., Ye, L., Huang, H., He, X., Tong, W.G., Ross, J., Haug, J., Johnson, T., Feng, J.Q., Harris, S., Wiedemann, L.M., Mishina, Y. and Li, L. (2003) Identification of the haematopoietic stem cell niche and control of the niche size. Nature, 425, 836-841. doi:10.1038/nature02041

[2]   Bruder, S.P., Fink, D.J. and Caplan, A.I. (1994) Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy. Journal of Cellular Biochemistry, 56, 283-294. doi:10.1002/jcb.240560303

[3]   Pereira, R.F., Halford, K.W., O’Hara, M.D., Leeper, D.B., Sokolov, B.P., Pollard, M.D., Bagasra, O. and Prockop, D.J. (1995) Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proceedings of the National Academy of Sciences of the USA, 92, 4857-4861. doi:10.1073/pnas.92.11.4857

[4]   Horwitz, E.M., Prockop, D.J., Fitzpatrick, L.A., Koo, W.W., Gordon, P.L., Neel, M., Sussman, M., Orchard, P., Marx, J.C., Pyeritz, R.E. and Brenner, M.K. (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nature Medicine, 5, 309-313. doi:10.1038/6529

[5]   Koc, O.N., Gerson, S.L., Cooper, B.W., Dyhouse, S.M., Haynesworth, S.E., Caplan, A.I. and Lazarus, H.M. (2000) Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. Journal of Clinical Oncology, 18, 307-316.

[6]   Le Blanc, K. and Ringden, O. (2005) Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation, 11, 321-334. doi:10.1016/j.bbmt.2005.01.005

[7]   Le Blanc, K., Frassoni, F., Ball, L., Locatelli, F., Roelofs, H., Lewis, I., Lanino, E., Sundberg, B., Bernardo, M.E., Remberger, M., Dini, G., Egeler, R.M., Bacigalupo, A., Fibbe, W., Ringden, O. and Developmental Committee of the European Group for Blood and Marrow Transplantation (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: A phase II study. Lancet, 371, 1579-1586. doi:10.1016/S0140-6736(08)60690-X

[8]   Tyndall, A. and Uccelli, A. (2009) Multipotent mesenchymal stromal cells for autoimmune diseases: Teaching new dogs old tricks. Bone Marrow Transplant, 43, 821-828. doi:10.1038/bmt.2009.63

[9]   Kobayashi, N., Yasu, T., Ueba, H., Sata, M., Hashimoto, S., Kuroki, M., Saito, M. and Kawakami, M. (2004) Mechanical stress promotes the expression of smooth muscle-like properties in marrow stromal cells. Exp Hematol, 32, 1238-1245. doi:10.1016/j.exphem.2004.08.011

[10]   Falanga, V., Iwamoto, S., Chartier, M., Yufit, T., Butmarc, J., Kouttab, N., Shrayer, D. and Carson, P. (2007) Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds. Tissue Engineering, 13, 1299-1312. doi:10.1089/ten.2006.0278

[11]   Semont, A., Francois, S., Mouiseddine, M., Francois, A., Sache, A., Frick, J., Thierry, D. and Chapel, A. (2006) Mesenchymal stem cells increase self-renewal of small intestinal epithelium and accelerate structural recovery after radiation injury. Advances in Experimental Medicine and Biology, 585, 19-30. doi:10.1007/978-0-387-34133-0_2

[12]   Li, Y., Chen, J., Chen, X.G., Wang, L., Gautam, S.C., Xu, Y.X., Katakowski, M., Zhang, L.J., Lu, M., Janakiraman, N. and Chopp, M. (2002) Human marrow stromal cell therapy for stroke in rat: Neurotrophins and functional recovery. Neurology, 59, 514-523.

[13]   Laflamme, M.A. and Murry, C.E. (2005) Regenerating the heart. Nature Biotechnology, 23, 845-856. doi:10.1038/nbt1117

[14]   Tang, Y.L. (2005) Autologous mesenchymal stem cells for post-ischemic myocardial repair. Methods in Molecular Medicine, 112, 183-192.

[15]   Da Silva Meirelles, L., Chagastelles, P.C. and Nardi, N.B. (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. Journal of Cell Science, 119, 2204-2213. doi:10.1242/jcs.02932

[16]   Sudo, K., Kanno, M., Miharada, K., Ogawa, S., Hiroyama, T., Saijo, K. and Nakamura, Y. (2007) Mesenchymal progenitors able to differentiate into osteogenic, chondrogenic, and/or adipogenic cells in vitro are present in most primary fibroblast-like cell populations. Stem Cells, 25, 1610-1617. doi:10.1634/stemcells.2006-0504

[17]   Pilgaard, L., Lund, P., Rasmussen, J.G., Fink, T. and Zachar, V. (2008) Comparative analysis of highly defined proteases for the isolation of adipose tissue-derived stem cells. Regenerative Medicine, 3, 705-715. doi:10.2217/17460751.3.5.705

[18]   Phinney, D.G. and Prockop, D.J. (2007) Concise review: Mesenchymal stem/multipotent stromal cells: The state of transdifferentiation and modes of tissue repair—current views. Stem Cells, 25, 2896-2902. doi:10.1634/stemcells.2007-0637

[19]   Phinney, D.G., Kopen, G., Isaacson, R.L. and Prockop, D.J. (1999) Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice: Variations in yield, growth, and differentiation. Journal of Cellular Biochemistry, 72, 570-585. doi:10.1002/(SICI)1097-4644(19990315)72:4<570::AID-JCB12>3.0.CO;2-W

[20]   Shen, F.H., Visger, J.M., Balian, G., Hurwitz, S.R. and Diduch, D.R. (2002) Systemically administered mesenchymal stromal cells transduced with insulin-like growth factor-I localize to a fracture site and potentiate healing. Journal of Orthopaedic Trauma, 16, 651-659. doi:10.1097/00005131-200210000-00007

[21]   Klarmann, K., Ortiz, M., Davies, M. and Keller, J.R. (2003) Identification of in vitro growth conditions for c-Kit-negative hematopoietic stem cells. Blood, 102, 3120-3128. doi:10.1182/blood-2003-04-1249

[22]   Crouse, D.A., Mann, S.L. and Sharp, J.G. (1984) Segregation and characterization of lymphohematopoietic stromal elements. Kroc Found Ser Journal, 18, 211-231.

[23]   Kessinger, A., O’Kane Murphy, B., Jackson, J.D. and Sharp, J.G. (2005) An ex vivo model of hematopoietic stem cell mobilization. Cytotherapy, 7, 463-469. doi:10.1080/14653240500361418

[24]   Pirruccello, S.J., Jackson, J.D., Lang, M.S., DeBoer, J., Mann, S., Crouse, D., Vaughan, W.P., Dicke, K.A. and Sharp, J.G. (1992) OMA-AML-1: A leukemic myeloid cell line with CD34+ progenitor and CD15+ spontaneously differentiating cell compartments. Blood, 80, 1026-1032.

[25]   Ho, A.D., Wagner, W. and Franke, W. (2008) Heterogeneity of mesenchymal stromal cell preparations. Cytotherapy, 10, 320-330. doi:10.1080/14653240802217011

[26]   Fu, X., He, Y., Xie, C. and Liu, W. (2008) Bone marrow mesenchymal stem cell transplantation improves ovarian function and structure in rats with chemotherapy-induced ovarian damage. Cytotherapy, 10, 353-363. doi:10.1080/14653240802035926

[27]   Abe, S., Lauby, G., Boyer, C., Rennard, S.I. and Sharp, J.G. (2003) Transplanted BM and BM side population cells contribute progeny to the lung and liver in irradiated mice. Cytotherapy, 5, 523-533. doi:10.1080/14653240310003576

 
 
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