Title: The superior regenerative potential of Mesangiogenic Progenitor Cells

Abstract:

Statement of the Problem: Even if an increased efficacy in cell isolation, expansion, and characterization leads to a consistent number of studies applying adult multipotent cells isolated from different tissues in various disease models, most of the clinical and pre-clinical investigations showed disappointing outcomes, related to the lack or inefficient vascularization of the new-formed tissue. Taking these considerations into account, MPC's power to couple melanogenesis and angiogenesis highlights their tissue regenerative potential and clinical value with particular reference to tissue engineering.
Methodology: We have isolated and compared MPCs from human bone marrow (hBM), a human stromal vascular fraction (hSVF) of adipose tissue, and human umbilical cord blood. We have also evaluated their differentiating potential. Flow cytometry and cell sorting have been performed to characterize the different populations.
Findings: MPCs are tissue-specific and can be isolated exclusively from hBM-mononuclear cells. MPCs can generate exponentially growing MSC cultures and in addition, MPCs retained angiogenic potential, suggesting the term "mesangiogenic". We also demonstrated a hierarchical multi-step model of mesenchymal differentiation with at least three different populations of multi-potent cells. Cell sorting experiments showed that a highly specific hBM subpopulation, described as Pop#8 and identified by the CD64brightCD31brightCD14negCD45dim phenotype, represents the only hBM subpopulation able to generate MPCs in culture under selective conditions.
Conclusion & Significance: We hypothesized that the suspected superior performances of hBM-MSCs in tissue regeneration could be explained by the presence of MPCs and/or their progenitors. It is reasonable to hypothesize that these cells could trigger new blood vessel formation in the early phases coupled with the essential chondrogenic and osteogenic differentiation capability. MPCs are found at frequencies from one to two logs higher than other MSC progenitors described in hBM. Consequently, millions of MPCs could be easily isolated, starting from 10-15 ml of fresh hBM in 4-6 days by applying a cheap and GMP-compliant culture method without the need for cell expansion. In summary, MPCs represent a valuable cell population for the proof of new concepts in tissue engineering, where neo-vascularization plays a crucial role in the establishment of successful therapies.

Biography:

Serena Barachini has a degree in Biology and a Ph.D. in Experimental Medicine from the University of Rome where she worked for six years in the lab of Tumor Immunology and Cell Therapy and she had attended a Postgraduate School in Clinical Pathology at the Hospital of Pisa where she was active in on-hematology for five years. She is working with Prof. Iacopo Petrini in “Laboratory for Cell Therapy” at the University of Pisa, where she is coordinating a group of researchers. Her study focuses on the isolation of MSCs and MPCs in human bone marrow, cord blood, and adipose tissues. Her work also concerns the study of cancer stem cells isolated from hematological diseases, thymoma, and glioblastoma. In particular, she has expertise in 3D cultures, flows cytometry, and cell sorting combined with molecular and cell biology techniques, applied in research projects concerning human stem cells both in tissue repair and cancers.