The Role of Collagen Type I on Hematopoietic and Mesenchymal Stem Cells Expansion and Differentiation

Abstract

The three dimensional scaffold of the bone marrow (BM) niches is composed of various elements including extracellular matrix proteins and cell types, such as collagen type I (Col I) and stroma cells. Interaction of stem cells with their microenvironment is important for their regulation. In the marrow, Col I is mostly localized in the endosteal regions. The objective of this work was to investigate the role of Col I in the regulation of Hematopoietic Stem Cells (HSC) and Mesenchymal Stem Cells (MSC) growth. Col I was extracted from rat tail tendons and its purity confirmed. Human BM MSCs and umbilical cord blood (UCB) CD34+cells were used as Stem Cell sources. MSCs were cultured in medium with serum while CB CD34+cells were cultured without serum with cytokines. The impact of increasing concentrations of Col I (0-50 µg mL-1for coating) on the growth of Hematopoietic Progenitor Cells (HPC) and MSCs was investigated by cytometry, microscopy and clonogenic progenitor assays. Only a minority of CD34+cells expressed the Col I receptor α2β1prior to culture, while the opposite was observed when hematopoietic cells were placed in culture. Col I coated surfaces reduced the expansion of hematopoietic cells by 25% compared to control, while expansions of myeloid and MK progenitors were either unchanged or negatively affected by Col I, respectively. The differentiation of HPCs was also affected on Col I as demonstrated by differences in the frequencies of various cell lineages, such as CD34+cells, megakaryocytes (MK), erythrocytes and others. In contrast to HPCs, Col I surfaces increased MSCs proliferation but had little impact on osteoblasts derived from MSCs. Taken together, this study provides new insights into the regulatory activities of Col I on Stem Cells residing in the marrow.