Proliferative and chondrogenic potential of mesenchymal stromal cells from pluripotent and bone marrow cells
Irene Sfougataki1,2, Ioanna Varela1, Kalliope Stefanaki3, Angeliki Karagiannidou1, Maria G. Roubelakis4, Vasiliki Kalodimou5, Ioanna Papathanasiou6, Joanne Traeger-Synodinos7, Sofia Kitsiou-Tzeli7, Emmanuel Kanavakis8, Vasiliki Kitra1, Aspasia Tsezou6, Maria Tzetis7 and Evgenios Goussetis1
1Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, 2Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Aghia Sophia Children's Hospital, 3Department of Histopathology, Aghia Sophia Children's Hospital, 4Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, 5Flow Cytometry-Research and Regenerative Medicine Department, IASO Hospital, Athens, 6Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessally, Thessally, 7Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens and 8Genesis Genoma Lab, Genetic diagnosis, Clinical Genetics and Research, Chalandri, Greece
Offprint requests to: Irene Sfougataki, PhD, Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Levadias 8, 11527 Athens, Greece. e-mail : irene_sf_@hotmail.com
Summary. Introduction. Mesenchymal stromal cells (MSCs) can be derived from a wide range of fetal and adult sources including pluripotent stem cells (PSCs). The properties of PSC-derived MSCs need to be fully characterized, in order to evaluate the feasibility of their use in clinical applications. PSC-MSC proliferation and differentiation potential in comparison with bone marrow (BM)-MSCs is still under investigation. The objective of this study was to determine the proliferative and chondrogenic capabilities of both human induced pluripotent stem cell (hiPSC-) and embryonic stem cell (hESC-) derived MSCs, by comparing them with BM-MSCs.
Methods. MSCs were derived from two hiPSC lines (hiPSC-MSCs), the well characterized Hues9 hESC line (hESC-MSCs) and BM from two healthy donors (BM-MSCs). Proliferation potential was investigated using appropriate culture conditions, with serial passaging, until cells entered into senescence. Differentiation potential to cartilage was examined after in vitro chondrogenic culture conditions.
Results. BM-MSCs revealed a fold expansion of 1.18x105 and 2.3x105 while the two hiPSC-MSC lines and hESC-MSC showed 5.88x1010, 3.49x108 and 2.88x108, respectively. Under chondrogenic conditions, all MSC lines showed a degree of chondrogenesis. However, when we examined the formed chondrocyte micromasses by histological analysis of the cartilage morphology and immunohistochemistry for the chondrocyte specific markers Sox9 and Collagen II, we observed that PSC-derived MSC lines had formed pink rather than hyaline cartilage, in contrast to BM-MSCs.
Conclusion. In conclusion, MSCs derived from both hESCs and hiPSCs had superior proliferative capacity compared to BM-MSCs, but they were inefficient in their ability to form hyaline cartilage. Histol Histopathol 35, 1415-1426 (2020)
Key words: Mesenchymal Stromal Cells, Pluripotent Stem Cells, Bone Marrow, Cell Proliferation, Chondrogenesis
DOI: 10.14670/HH-18-259