BIOLOGICAL CHARACTERIZATION OF HUMAN MESENCHYMAL STEM CELLS AND THEIR USE IN REGENERATIVE THERAPIES
Human Mesenchymal Stem Cells (hMSC) is a stem cell population able to differentiate into bone, cartilage and fat cells. The lack of appropriate cell surface markers to identify the Stem Cells within the hMSC population has prevented from establishing their hierarchy, identifying the Stem Cells and the precursors of a given cell lineage. Nonetheless, hMSC from different origins are being used for regenerative therapies.
Comparison of hMSC from Periodontal Ligament and Gingiva:
We compared the characteristics of undifferentiated human mesenchymal stem cells (hMSC) from either periodontal ligament or gingival origin, to establish the basis for the future use of these cells on regenerative therapies. Gingiva-derived mesenchymal stem cells (GMSCs) were obtained from de-epithelialized gingival biopsies, enzymatically digested and expanded in conditions of exponential growth. Their growth characteristics, phenotype and differentiation ability were compared with those of periodontal ligament-derived mesenchymal stem cells (PDLMSCs). Both PDLMSCs and GMSCs displayed a MSC-like phenotype and were able to differentiate into osteoblasts, chondroblasts and adipocytes. These cells where genetically stable following in vitro expansion, and did not generate tumors when implanted in immunocompromised mice. Furthermore, under suboptimal growth conditions, GMSCs proliferated with higher rates than PDLMSCs. Thus, Stem cells derived from gingival biopsies represent bona-fide MSCs and have demonstrated genetic stability and lack of tumorigenicity (1).
We participate on a phase I clinical trial aiming to regenerate bone defects on individuals affected of periodontitis (ISRCTN registry 13093912 doi: 10.1186/ISRCTN13093912), where we established the conditions for the isolation and in vitro growth of the PDLMSCs used for the regenerative therapy.
Basic Biology of hMSC:
Human mesenchymal stem cells (hMSC) from different origins (gingiva, periodontal ligament, fat, bone marrow) are being used to biologically characterize this complex cell population. Despite the lack of specific surface markers identifying MSCs, these are fibroblast-like cells attaching to plastic surfaces, with a phenotype CD73+CD90+CD105+CD34-CD45-HLA-DR-CD11b-CD19-, able to self-renew maintaining their multi-potentiality, that could differentiate into osteoblasts, adipocytes and chondrocyes. We are interested on analyzing their self-renewal ability and their potential to differentiate into bone, cartilage and fat, as well as to characterize their type of divisions (symmetric and asymmetric) aiming to establish their hierarchy. This will allow us to distinguish between the more undifferentiated cells from osteoblast-, adipocyte- and chondrocyte-precursors, which will be extremely useful for their use on regenerative therapies.
This project is being carried out in collaboration with M. Sanz, UCM, Madrid, Spain.
1. Santamaria, S., Sanchez, N., Sanz, M., and Garcia-Sanz, J. A. (2016) Comparison of periodontal ligament and gingiva-derived mesenchymal stem cells for regenerative therapies. Clin Oral Investig doi:10.1007/s00784-016-1867-3