Research areas
Human umbilical cord as an alternative source of mesenchymal stromal cells.
Bone marrow (BM) is the primary and most studied tissue source of mesenchymal stromal cells (MSCs). However, donor availability and the decline in function with increasing donor age are important limitations. We are working on the characterization of umbilical cord (UC) tissue as an attractive alternative source of MSCs for cell therapy. We found that UC-MSCs present higher levels of stromal progenitors and exhibit enhanced OCT4 expression compared with BM-MSCs. These biological properties of UC-MSCs may result from their neonatal tissue origin and are associated with improved regenerative potential. Interestingly, the epigenetic profile of MSCs at the OCT4 promoter restricts their differentiation capacity. This mechanism explains the multipotency of MSCs and their very low risk of tumor formation (if any) compared with embryonic stem cells. The use of UC-derived MSCs has significantly increased during the last years, both for research and clinical studies.
Mesenchymal stromal cells for cardiac regeneration.
We aim to understand the mechanisms mediating cardiac regeneration by mesenchymal stromal cells (MSCs). For about a decade, it was though that MSCs could fully differentiate into cardiomyocytes to replace the tissue lost after acute myocardial infarction. However, new lines of evidence have pointed to the paracrine action of MSCs, which can engender cardiac repair. For example, MSC-therapy produces a switch from the infiltration of pro-inflammatory to anti-inflammatory macrophages at the infarct site. Partial differentiation of MSCs into cardiomyocytes also seems a crucial mechanism for shaping their secretome and potentiating regeneration.
Mesenchymal stromal cells for donor lung preservation and recovery.
Lung transplantation is the only treatment available for people living with severe lung disease. The high number of patients awaiting transplantation is related to the lack of donors and the low percentage of lungs deemed acceptable for implantation. Thus, implementing new therapeutic strategies for organ preservation and recovery may significantly reduce the current shortage of donor’s lungs. In this regard, we are studying whether the anti-inflammatory and immunosuppressive effect of human umbilical cord-derived mesenchymal stromal (UC-MSCs) may help increase lung availability by improving organ preservation and recovery.
Anti-inflammatory extracellular vesicles from mesenchymal stromal cells.
More recently, our research focused on the isolation and characterization of extracellular vesicles (EVs) from mesenchymal stromal cells (MSCs). We developed a clinically scalable chromatographic procedure for the isolation of anti-inflammatory EVs. Moreover, we established an in vitro macrophage functional assay that makes it possible to rank different EV preparations by their anti-inflammatory activity. Of note, this ranking predicts their efficacy in suppressing LPS-stimulated inflammation in mice. EVs are a novel alternative to cell-based therapies, and we are applying them for tissue regeneration and organ preservation.