Abstract
Tissue engineering is a novel technology developed for the regeneration of tissue using cultured cells, scaffolds, and osteogenic inductive signals. Bone marrow stromal cells (also designated as multipotent mesenchymal stromal cells, mesenchymal stem cells, or MSCs) have been the most commonly used cell source for bone tissue engineering. For efficient bone tissue engineering, the cells must be expanded in vitro and induced into osteogenic cells with an osteoinductive reagent such as dexamethasone. Recently, physiological factors such as bone morphogenetic proteins have been shown to induce the osteogenic lineage of bone marrow stromal cells. Osteogenic reagents have been widely used in both basic and clinical studies. However, it is apparent that the cellular responses to those reagents have been heterogeneous in human cells compared with animal cells, which possess a more uniform genetic background. Since the clinical use of those factors will increase further in the cases of orthopaedic applications and in the context of tissue engineering, these responses could be a serious problem in the future. In this chapter, the heterogeneous response of human bone marrow stromal cells to those inductive factors is discussed with reference to possible underlying mechanisms.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Agata H, Asahina I, Watanabe N, Ishii Y, Kubo N, Ohshimam S, Yamazaki M, Tojo A, Kagami H (2010) Characteristic change and loss of in vivo osteogenic abilities of human bone marrow stromal cells during passage. Tissue Eng Part A 16:663–673
Aubin JE (1999) Osteoprogenitor cell frequency in rat bone marrow stromal populations: role for heterotypic cell-cell interactions in osteoblast differentiation. J Cell Biochem 72:396–410
Birkenhäger JC, van der Heul RO, Smeenk D, van der Sluys Veer J, van Seters AP (1967) Bone changes associated with glucocorticoid excess. Proc R Soc Med 60:1134–1136
Burkus JK, Dorchak JD, Sanders DL (2003) Radiographic assessment of interbody fusion using recombinant human bone morphogenetic protein type 2. Spine 28:372–377
Chen X, Kidder LS, Lew WD (2002) Osteogenic protein-1 induced bone formation in an infected segmental defect in the rat femur. J Orthop Res 20:142–150
De Biase P, Capanna R (2005) Clinical applications of BMPs. Injury 36:S43–S46
Diefenderfer DL, Osyczka AM, Reilly GC, Leboy PS (2003) BMP responsiveness in human mesenchymal stem cells. Connect Tissue Res 44:305–311
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317
Fedde KN, Blair L, Silverstein J, Coburn SP, Ryan LM, Weinstein RS, Waymire K, Narisawa S, Millán JL, MacGregor GR, Whyte MP (1999) Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia. J Bone Miner Res 14:2015–2026
Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3:393–403
Harrison JR, Woitge HW, Kream BE (2002) Genetic approaches to determine the role of glucocorticoid signaling in osteoblasts. Endocrine 17:37–42
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 KJ, Itoh T, Kotake S (1997) Effects of recombinant human bone morphogenetic protein-2 on human bone marrow cells cultured with various biomaterials. J Biol Chem 35:279–285
Kuznetsov SA, Krebsbach PH, Satomura K, Kerr J, Riminucci M, Benayahu D, Robey PG (1997) Single-colony derived strains of human marrow stromal fibroblasts form bone after transplantation in vivo. J Bone Miner Res 12:1335–1347
Kwong FN, Harris MB (2008) Recent developments in the biology of fracture repair. J Am Acad Orthop Surg 16:619–625
Lecanda F, Avioli LV, Cheng SL (1997) Regulation of bone matrix protein expression and induction of differentiation of human osteoblasts and human bone marrow stromal cells by bone morphogenetic protein-2. J Cell Biochem 67:386–396
Li J, Khavandgar Z, Lin SH, Murshed M (2011) Lithium chloride attenuates BMP-2 signaling and inhibits osteogenic differentiation through a novel WNT/GSK3-independent mechanism. Bone 48:321–331
McCulloch CAG, Tenenbaum HC (1986) Dexamethasone induces proliferation and terminal differentiation of osteogenic cells in tissue culture. Anat Rec 215:397–402
Mendes SC, Tibbe JM, Veenhof M, Bakker K, Both S, Platenburg PP, Oner FC, de Bruijn JD, van Blitterswijk CA (2002) Bone tissue-engineered implants using human bone marrow stromal cells: Effect of culture conditions and donor age. Tissue Eng 8:911–920
Mizuno D, Agata H, Furue H, Kimura A, Narita Y, Watanabe N, Ishii Y, Ueda M, Tojo A, Kagami H (2010) Limited but heterogeneous osteogenic response of human bone marrow mesenchymal stem cells to bone morphogenetic protein-2 and serum. Growth Factors 28:34–43
Osyczka AM, Leboy PS (2005) Bone morphogenetic protein regulation of early osteoblast genes in human marrow stromal cells is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling. Endocrinology 146:3428–3437
Osyczka AM, Diefenderfer DL, Bhargave G, Leboy PS (2004) Different effects of BMP-2 on marrow stromal cells from human and rat bone. Cell Tissues Organs 176:109–119
Phinney DG, Kopen G, Righter W, Webster S, Tremain N, Prockop DJ (1999) Donor variation in the growth properties and osteogenic potential of human marrow stromal cells. J Cell Biochem 75:424–436
Reddi AH (1998) Initiation of fracture repair by bone morphogenetic proteins. Clin Orthop Relat Res 355S:s66–s72
Reilly GC, Radin S, Chen AT, Ducheyne P (2007) Differential alkaline phosphatase responses of rat and human bone marrow derived mesenchymal cells to 45S5 bioactive glass. Biomaterials 28:4091–4097
Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I, Tagliafico E, Ferrari S, Robey PG, Riminucci M, Bianco P (2007) Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131:324–336
Salem HK, Thiemermann C (2010) Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 28:585–596
Schwarz F, Ferrari D, Sager M, Herten M, Hartig B, Becker J (2009) Guided bone regeneration using rhGDF-5- and rhBMP-2-coated natural bone mineral in rat calvarial defects. Clin Oral Implants Res 1219–1230
Sheehan JP, Sheehan JM, Seeherman H, Quigg M, Helm GA (2003) The safety and utility of recombinant human bone morphogenetic protein-2 for cranial procedures in a nonhuman primate model. J Neurosurg 98:125–130
Siddappa R, Licht R, van Blitterswijk C, de Boer J (2007) Donor variation and loss of multipotency during in vitro expansion of human mesenchymal stem cells for bone tissue engineering. J Orthop Res 25:1029–1041
Singhatanadgit W, Mordan N, Salih V, Olsen I, (2008) Changes in bone morphogenic protein receptor-IB localization regulate osteogenic responses of human bone cells to bone morphogenic protein-2. Int J Biochem Cell Biol 40:2854–2864
Swiontkowski MF, Aro HT, Donell S, Esterhai JL, Goulet J, Jones A, Kregor PJ, Nordsletten L, Paiement G, Patel A (2006) Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies. J. Bone Joint Surg Am 88:1258–1265
Tamura Y, Okinaga H, Takami H (2004) Glucocorticoid-induced osteoporosis. Biomed Pharmacother 58:500–504
Urist MR (1965) Bone formation by autoinduction. Science 150:893–899
Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102:274–282
Ylöstalo J, Bazhanov N, Prockop DJ (2008) Reversible commitment to differentiation by human multipotent stromal cells in single-cell-derived colonies. Exp Hematol 36:1390–1402
Acknowledgement
The authors with to thank Ms. Sachiko Sawada for the technical assistance.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Kagami, H., Agata, H., Sumita, Y., Tojo, A. (2012). Heterogeneous Responses of Human Bone Marrow Stromal Cells (Multipotent Mesenchymal Stromal Cells) to Osteogenic Induction. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 2. Stem Cells and Cancer Stem Cells, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2016-9_33
Download citation
DOI: https://doi.org/10.1007/978-94-007-2016-9_33
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-2015-2
Online ISBN: 978-94-007-2016-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)