Podocalyxin-like protein 1 is a relevant marker for human c-kit^poscardiac stem cells

Abstract

Cardiac progenitor cells (CPCs) from adult myocardium offer an alternative cell therapy approach for ischaemic heart disease. Improved clinical performance of CPCs in clinical trials requires a comprehensive definition of their biology and specific interactions with the environment. In this work we characterize specific human CPC surface markers and study some of their related functions. c-kit(pos) human CPCs (hCPCs) were characterized for cell surface marker expression, pluripotency, early and late cardiac differentiation markers and therapeutic activity in a rat model of acute myocardial infarction. The results indicate that hCPCs are a mesenchymal stem cell (MSC)-like population, with a similar immunoregulatory capacity. A partial hCPC membrane proteome was analysed by liquid chromatography-mass spectrometry/mass spectrometry and 36 proteins were identified. Several, including CD26, myoferlin and podocalyxin-like protein 1 (PODXL), have been previously described in other stem-cell systems. Suppression and overexpression analysis demonstrated that PODXL regulates hCPC activation, migration and differentiation; it also modulates their local immunoregulatory capacity. Therefore, hCPCs are a resident cardiac population that shares many features with hMSCs, including their capacity for local immunoregulation. Expression of PODXL appears to favour the immature state of hCPCs, while its downregulation facilitates their differentiation. Copyright © 2016 John Wiley & Sons, Ltd.

miR-133a Enhances the Protective Capacity of Cardiac Progenitors Cells after Myocardial Infarction

“…CPCs from adult mouse hearts accounted for 7%–20% of the myocyte-depleted small cells from the myocardium ( Figures S1 A and S1B available online) and endowed cardiac, endothelial, and smooth-muscle differentiation capacity ( Figures S1 C and S2 ). In addition, mouse CPCs also demonstrated MSC-like differential potential ( Figures S1 D and S1E) as previously shown for human counterparts ( Moscoso et al., 2013 ). miR-1 and miR-133a expression was under the detection level in undifferentiated CPCs, but exposure to cardiac differentiation conditions ( Figure 1 A) or coculture with neonatal rat cardiomyocytes (NRCMs; Figure 1 B) progressively increased the expression of miR-1 and miR-133a.…”

Exploring analytical proteomics platforms toward the definition of human cardiac stem cells receptome

“…1; Supporting Information Table T2). Eighty of the proteins identified were also found in our MALDI-TOF/TOF experiment, and 18 were already described in Moscoso et al study [13]. CD71, MMP-14, and a few others were consistently identified.…”

“…Other attempts for partial hCSC receptome characterization using specific proteomics techniques have been previously reported. Moscoso et al described an approach based on biotinylation of plasma membrane proteins where only 36 proteins were identified . Moreover, most of the proteins listed are just plasma membrane associated or contained a single transmembrane domain (TMD) and only a few receptors were identified.…”

“…Enriched plasma membrane fractions: hCSC isolation and cell characterization were previously reported . After expansion, cells were harvested (passage 6/7) by scraping and washed twice with PBS.…”

Detection of Quiescent Radioresistant Epithelial Progenitors in the Adult Thymus

“…Two genes specifically upregulated in UEA1 – LRCs are involved in the regulation of stem cell activity in several tissues: Podxl and Ptprz1 (Figure 6 C). Podxl , a marker of cardiac, hematopoietic and mesenchymal stem cells, is involved in the maintenance of the immature state in cardiac stem cells and its downregulation facilitates their differentiation ( 46 – 48 ). Ptprz1 is expressed in human embryonic stem cells and is downregulated during differentiation.…”