Identification of Common Pathways Mediating Differentiation of Bone Marrow‐ and Adipose Tissue‐Derived Human Mesenchymal Stem Cells into Three Mesenchymal Lineages

Mesenchymal stem cells derived from human bone marrow (hBMSCs) and human adipose tissue (hAMSCs) represent a useful source of progenitor cells for cell therapy and tissue engineering. However, it is not clear what the similarities and differences between them are. Like hBMSCs, hAMSCs can differentiate into osteogenic, adipogenic, and chondrogenic cells. Whether MSCs derived from different tissue sources represent fundamentally similar or different cell types is not clear. Given the possible different sources of MSCs for cell therapy, a comprehensive comparison of the different MSCs would be very useful. Here, we compared the transcriptome profile of hAMCS and hBMSCs during directed differentiation into bone, cartilage, and fat. Our data revealed considerable similarities between bone marrow‐derived MSCs (BMSCs) and adipose tissue‐derived MSCs (AMSCs). We uncovered an interesting bifurcation of pathways in both BMSCs and AMSCs, in which osteogenesis and adipogenesis appear to be linked in a differentiation branch separate from chondrogenesis. Our data suggest that although a set of common genes may be needed for early differentiation into all three lineages, a different set of signature genes is associated with maturation into fully differentiated cells. The recruitment of different late differentiation factors explains and supports our conclusion that BMSCs differentiate more efficiently into bone and cartilage, whereas AMSCs differentiate better into adipocytes. This study not only generated a rich database for continuing molecular characterization of various MSCs but also provided a rational basis for assessing qualities of MSCs from different sources for the purpose of cell‐based therapy and tissue engineering.

[1]  Wei Tang,et al.  Molecular and cellular characterization during chondrogenic differentiation of adipose tissue-derived stromal cells in vitro and cartilage formation in vivo , 2008, Cell Research.

[2]  E Jones,et al.  Growing bone and cartilage. The role of mesenchymal stem cells. , 2006, The Journal of bone and joint surgery. British volume.

[3]  J. Pesquero,et al.  High expression of human carboxypeptidase M in Pichia pastoris: purification and partial characterization. , 2006, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[4]  F. Guilak,et al.  Clonal analysis of the differentiation potential of human adipose‐derived adult stem cells , 2006, Journal of cellular physiology.

[5]  Mahidhar M. Durbhakula,et al.  Chondrogenic potential of progenitor cells derived from human bone marrow and adipose tissue: A patient‐matched comparison , 2005, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[6]  Y. Sakaguchi,et al.  Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. , 2005, Arthritis and rheumatism.

[7]  J. Fletcher,et al.  Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes , 2005, Oncogene.

[8]  L. Pénicaud,et al.  Immunomodulatory effect of human adipose tissue‐derived adult stem cells: comparison with bone marrow mesenchymal stem cells , 2005, British journal of haematology.

[9]  G. Sukhikh,et al.  Comparison of Mesenchymal Stem Cells Obtained from Different Human Tissues , 2005, Bulletin of Experimental Biology and Medicine.

[10]  Kenichi Yoshida,et al.  The Promyelotic Leukemia Zinc Finger Promotes Osteoblastic Differentiation of Human Mesenchymal Stem Cells as an Upstream Regulator of CBFA1*[boxs] , 2005, Journal of Biological Chemistry.

[11]  P. Neame,et al.  The link proteins , 1993, Experientia.

[12]  Bernward Klocke,et al.  Analysis of transcriptional regulation of the small leucine rich proteoglycans. , 2004, Molecular vision.

[13]  L. R. Harris,et al.  A novel retinoic acid-response element requires an enhancer element mediator for transcriptional activation. , 2004, The Biochemical journal.

[14]  T. Borrás,et al.  Genes expressed in the human trabecular meshwork during pressure‐induced homeostatic response , 2004, Journal of cellular physiology.

[15]  Y. Bae,et al.  Characterization and Expression Analysis of Mesenchymal Stem Cells from Human Bone Marrow and Adipose Tissue , 2004, Cellular Physiology and Biochemistry.

[16]  P. Byers,et al.  Gene Targeting in Stem Cells from Individuals with Osteogenesis Imperfecta , 2004, Science.

[17]  Daniel A. De Ugarte,et al.  Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow. , 2003, Immunology letters.

[18]  K. Kraus,et al.  Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. , 2003, The Journal of bone and joint surgery. American volume.

[19]  Brendan H. Lee,et al.  Type X collagen gene regulation by Runx2 contributes directly to its hypertrophic chondrocyte–specific expression in vivo , 2003, The Journal of cell biology.

[20]  Joyce Cheung-Flynn,et al.  The FK506-binding immunophilin FKBP51 is transcriptionally regulated by progestin and attenuates progestin responsiveness. , 2003, Endocrinology.

[21]  Huilin Qi,et al.  Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[22]  K. Xia,et al.  In vitro chondrogenesis of human bone marrow-derived mesenchymal progenitor cells in monolayer culture: activation by transfection with TGF-beta2. , 2003, Tissue & cell.

[23]  Min Zhu,et al.  Human adipose tissue is a source of multipotent stem cells. , 2002, Molecular biology of the cell.

[24]  Takashi Murakami,et al.  Increased expression of dermatopontin mRNA in the infarct zone of experimentally induced myocardial infarction in rats: comparison with decorin and type I collagen mRNAs , 2002, Basic Research in Cardiology.

[25]  L. Muul,et al.  Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Darwin J. Prockop,et al.  In vitro cartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[27]  W. Pratt,et al.  Evidence for a Mechanism of Repression of Heat Shock Factor 1 Transcriptional Activity by a Multichaperone Complex* , 2001, The Journal of Biological Chemistry.

[28]  H. Lorenz,et al.  Multilineage cells from human adipose tissue: implications for cell-based therapies. , 2001, Tissue engineering.

[29]  Eric P. Hoffman,et al.  Expression Profiling in the Muscular Dystrophies Identification of Novel Aspects of Molecular Pathophysiology , 2000 .

[30]  F. Bleicher,et al.  Expression of the small leucine-rich proteoglycan osteoadherin/osteomodulin in human dental pulp and developing rat teeth. , 2000, Bone.

[31]  M. Ko,et al.  Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[32]  P. Pandolfi,et al.  Plzf regulates limb and axial skeletal patterning , 2000, Nature Genetics.

[33]  R Cancedda,et al.  Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. , 2000, Journal of cell science.

[34]  J. Hiscott,et al.  Posttranslational regulation of IRF-4 activity by the immunophilin FKBP52. , 2000, Immunity.

[35]  E. Rassart,et al.  Apolipoprotein D. , 2000, Biochimica et biophysica acta.

[36]  O. Okamoto,et al.  Dermatopontin expression is decreased in hypertrophic scar and systemic sclerosis skin fibroblasts and is regulated by transforming growth factor-beta1, interleukin-4, and matrix collagen. , 1999, The Journal of investigative dermatology.

[37]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[38]  R. Lyle,et al.  Molecular regulation of adipocyte differentiation. , 1999, Seminars in cell & developmental biology.

[39]  Yoshihiko Yamada,et al.  Mice lacking link protein develop dwarfism and craniofacial abnormalities , 1999, Nature Genetics.

[40]  M. Caboche,et al.  Mutation in the Arabidopsis PASTICCINO1Gene, Which Encodes a New FK506-Binding Protein-Like Protein, Has a Dramatic Effect on Plant Development , 1998, Molecular and Cellular Biology.

[41]  S. Ness,et al.  Point mutations in v-Myb disrupt a cyclophilin-catalyzed negative regulatory mechanism. , 1998, Molecular cell.

[42]  M. Martin,et al.  Tissue distribution and abundance of human FKBP51, and FK506-binding protein that can mediate calcineurin inhibition. , 1997, Biochemical and biophysical research communications.

[43]  A. Bradley,et al.  Impaired energy homeostasis in C/EBP alpha knockout mice , 1995, Science.

[44]  B. Spiegelman,et al.  mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. , 1994, Genes & development.

[45]  T. Hardingham,et al.  The structure, function and turnover of aggrecan, the large aggregating proteoglycan from cartilage. , 1994, European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies.

[46]  P. Grimaldi,et al.  Cellular and molecular aspects of adipose tissue development. , 1992, Annual review of nutrition.

[47]  T. Doering,et al.  Tissue specific expression of p422 protein, a putative lipid carrier, in mouse adipocytes. , 1985, Biochemical and biophysical research communications.