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Pan-myeloid Differentiation of Human Cord Blood Derived CD34+ Hematopoietic Stem and Progenitor Cells
Published on: August 9, 2019
Mesangiogenic Progenitor Cells Derived from One Novel CD64(bright)CD31(bright)CD14(neg) Population in Human Adult
Simone Pacini1, Serena Barachini1, Marina Montali1
11 Hematology Division, Department of Clinical and Experimental Medicine, University of Pisa , Pisa, Italy .
Abstract:
Mesenchymal stromal cells (MSCs) have been the object of extensive research for decades, due to their intrinsic clinical value. Nonetheless, the unambiguous identification of a unique in vivo MSC progenitor is still lacking, and the hypothesis that these multipotent cells could possibly arise from different in vivo precursors has been gaining consensus in the last years. We identified a novel multipotent cell population in human adult bone marrow that we first named Mesodermal Progenitor Cells (MPCs) for the ability to differentiate toward the mesenchymal lineage, while still retaining angiogenic potential. Despite extensive characterization, MPCs positioning within the differentiation pathway and whether they can be ascribed as possible distinctive progenitor of the MSC lineage is still unclear. In this study, we describe the ex vivo isolation of one novel bone marrow subpopulation (Pop#8) with the ability to generate MPCs. Multicolor flow cytometry in combination with either fluorescence-activated cell sorting or magnetic-activated cell sorting were applied to characterize Pop#8 as CD64(bright)CD31(bright)CD14(neg). We defined Pop#8 properties in culture, including the potential of Pop#8-derived MPCs to differentiate into MSCs. Gene expression data were suggestive of Pop#8 in vivo involvement in hematopoietic stem cell niche constitution/maintenance. Pop#8 resulted over three logs more frequent than other putative MSC progenitors, corroborating the idea that most of the controversies regarding culture-expanded MSCs could be the consequence of different culture conditions that select or promote particular subpopulations of precursors.
Insights
Researchers identified a novel bone marrow subpopulation, Pop#8, capable of generating Mesodermal Progenitor Cells (MPCs). This finding offers new insights into the origins of Mesenchymal Stromal Cells (MSCs).
Area of Science:
- Stem Cell Biology
- Hematology
- Cellular Biology
Background:
- Mesenchymal Stromal Cells (MSCs) are extensively researched for clinical applications.
- The precise in vivo origin of MSCs remains unidentified, with growing evidence suggesting diverse precursors.
- Previous research has identified Mesodermal Progenitor Cells (MPCs) with multipotent differentiation and angiogenic potential.
Purpose of the Study:
- To isolate and characterize a novel bone marrow subpopulation (Pop#8) capable of generating MPCs.
- To elucidate the potential role of Pop#8 in the Mesenchymal Stromal Cell (MSC) lineage.
- To investigate the in vivo function and frequency of Pop#8.
Main Methods:
- Isolation of a novel bone marrow subpopulation (Pop#8).
- Characterization using multicolor flow cytometry and cell sorting (FACS/MACS).
- Assessment of differentiation potential of Pop#8-derived MPCs into MSCs.
- Gene expression analysis to infer in vivo function.
Main Results:
- Pop#8 was identified as CD64(bright)CD31(bright)CD14(neg).
- Pop#8 demonstrated the ability to generate MPCs, which could differentiate into MSCs.
- Gene expression data suggested Pop#8's involvement in the hematopoietic stem cell niche.
- Pop#8 was found to be over three logs more frequent than other putative MSC progenitors.
Conclusions:
- Pop#8 represents a novel progenitor population capable of generating Mesodermal Progenitor Cells (MPCs).
- The high frequency of Pop#8 supports its role as a significant precursor in the Mesenchymal Stromal Cell (MSC) lineage.
- Variability in culture-expanded MSCs may stem from the selection of distinct precursor subpopulations like Pop#8.
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