Mesengenic Differentiation: Comparison of Human and Rat Bone Marrow Mesenchymal Stem Cells

Background and Objectives: Cellular therapies using Mesenchymal Stem Cells (MSCs) represent a promising approach for the treatment of degenerative diseases, in particular for mesengenic tissue regeneration. However, before the approval of clinical trials in humans, in vitro studies must be performed aimed at investigating MSCs’ biology and the mechanisms regulating their proliferation and differentiation abilities. Besides studies on human MSCs (hMSCs), MSCs derived from rodents have been the most used cellular type for in vitro studies. Nevertheless, the transfer of the results obtained using animal MSCs to hMSCs has been hindered by the limited knowledge regarding the similarities existing between cells of different origins. Aim of this paper is to highlight similarities and differences and to clarify the sometimes reported different results obtained using these cells. Methods and Results: We compare the differentiation ability into mesengenic lineages of rat and human MSCs cultured in their standard conditions. Our results describe in which way the source from which MSCs are derived affects their differentiation potential, depending on the mesengenic lineage considered. For osteogenic and chondrogenic lineages, the main difference between human and rat MSCs is represented by differentiation time, while for adipogenesis hMSCs have a greater differentiation potential. Conclusions: These results on the one hand suggest to carefully evaluate the transfer of results obtained with animal MSCs, on the other hand they offer a clue to better apply MSCs into clinical practice.

[1]  M. Miloso,et al.  Human mesenchymal stem cells express neuronal markers after osteogenic and adipogenic differentiation , 2013, Cellular & Molecular Biology Letters.

[2]  M. Miloso,et al.  From cytogenomic to epigenomic profiles: monitoring the biologic behavior of in vitro cultured human bone marrow mesenchymal stem cells , 2012, Stem Cell Research & Therapy.

[3]  M. Miloso,et al.  Expression of Neural Markers by Undifferentiated Rat Mesenchymal Stem Cells , 2012, Journal of biomedicine & biotechnology.

[4]  I. Fischer,et al.  Secretion profile of human bone marrow stromal cells: donor variability and response to inflammatory stimuli. , 2010, Cytokine.

[5]  P. Tropel,et al.  Hypoxia increases Sca-1/CD44 co-expression in murine mesenchymal stem cells and enhances their adipogenic differentiation potential , 2010, Cell and Tissue Research.

[6]  H. Yoshikawa,et al.  Hypoxia responsive mesenchymal stem cells derived from human umbilical cord blood are effective for bone repair. , 2010, Stem cells and development.

[7]  M. Szczodry,et al.  Animal models for cartilage regeneration and repair. , 2010, Tissue engineering. Part B, Reviews.

[8]  Cláudia Lobato da Silva,et al.  Ex vivo expansion of human mesenchymal stem cells: A more effective cell proliferation kinetics and metabolism under hypoxia , 2009, Journal of cellular physiology.

[9]  M. Miloso,et al.  Monitoring the genomic stability of in vitro cultured rat bone-marrow-derived mesenchymal stem cells , 2009, Chromosome Research.

[10]  M. Martínez-Lorenzo,et al.  Phenotype and chondrogenic differentiation of mesenchymal cells from adipose tissue of different species , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[11]  Brunella Grigolo,et al.  Osteoarthritis treated with mesenchymal stem cells on hyaluronan-based scaffold in rabbit. , 2009, Tissue engineering. Part C, Methods.

[12]  Yufang Shi,et al.  Species Variation in the Mechanisms of Mesenchymal Stem Cell‐Mediated Immunosuppression , 2009, Stem cells.

[13]  M. Bhide,et al.  Beyond the Rat Models of Human Neurodegenerative Disorders , 2009, Cellular and Molecular Neurobiology.

[14]  G. Brook,et al.  Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression , 2009, BMC Neuroscience.

[15]  M. Kassem,et al.  The use of mesenchymal (skeletal) stem cells for treatment of degenerative diseases: Current status and future perspectives , 2009, Journal of cellular physiology.

[16]  Patrick J Prendergast,et al.  Hypoxia promotes chondrogenesis in rat mesenchymal stem cells: A role for AKT and hypoxia‐inducible factor (HIF)‐1α , 2008, Journal of cellular physiology.

[17]  A. Uccelli,et al.  Mesenchymal stem cells in health and disease , 2008, Nature Reviews Immunology.

[18]  C. Choong,et al.  PDGF, TGF-beta, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages. , 2008, Blood.

[19]  P. Martiat,et al.  Gene expression pattern of functional neuronal cells derived from human bone marrow mesenchymal stromal cells , 2008, BMC Genomics.

[20]  G. Reilly,et al.  Differential alkaline phosphatase responses of rat and human bone marrow derived mesenchymal stem cells to 45S5 bioactive glass. , 2007, Biomaterials.

[21]  Ramon Bragós,et al.  FGF-4 increases in vitro expansion rate of human adult bone marrow-derived mesenchymal stem cells , 2007, Growth factors.

[22]  O. Lee,et al.  In vitro hepatic differentiation of human mesenchymal stem cells , 2004, Hepatology.

[23]  Jueren Lou,et al.  Migration of Mesenchymal Stem Cells Through Cerebrospinal Fluid into Injured Spinal Cord Tissue , 2004, Spine.

[24]  B. Larson,et al.  Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential. , 2004, Blood.

[25]  E. Guinan,et al.  Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation , 2003, Transplantation.

[26]  M. Vingron,et al.  Gene expression profile of mouse bone marrow stromal cells determined by cDNA microarray analysis , 2003, Cell and Tissue Research.

[27]  G. Reilly,et al.  BMP Responsiveness in Human Mesenchymal Stem Cells , 2003, Connective tissue research.

[28]  Gene Kopen,et al.  Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice: Variations in yield, growth, and differentiation , 1999, Journal of cellular biochemistry.

[29]  D. Prockop Marrow Stromal Cells as Stem Cells for Nonhematopoietic Tissues , 1997, Science.

[30]  M. Orciani,et al.  Skin-derived mesenchymal stem cells: isolation, culture, and characterization. , 2013, Methods in molecular biology.

[31]  J. Domenech,et al.  Impaired differentiation potential of human trabecular bone mesenchymal stromal cells from elderly patients. , 2009, Cytotherapy.

[32]  M. Miloso,et al.  Mesenchymal stem cells cultured on a collagen scaffold: In vitro osteogenic differentiation. , 2007, Archives of oral biology.

[33]  R. Cortivo,et al.  Osteogenic and chondrogenic differentiation: comparison of human and rat bone marrow mesenchymal stem cells cultured into polymeric scaffolds. , 2007, European journal of histochemistry : EJH.

[34]  G. Tredici,et al.  GMP-grade preparation of biomimetic scaffolds with osteo-differentiated autologous mesenchymal stromal cells for the treatment of alveolar bone resorption in periodontal disease. , 2007, Cytotherapy.

[35]  D. Prockop,et al.  Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. , 2006, Cytotherapy.