Open AccessPharmacologically active microcarriers influence VEGF ‐A effects on mesenchymal stem cell survival
Author(s) -
Penna Claudia,
Perrelli MariaGiulia,
Karam JeanPierre,
Angotti Carmelina,
Muscari Claudio,
MonteroMenei Claudia N.,
Pagliaro Pasquale
Publication year - 2013
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01662.x
Subject(s) - mesenchymal stem cell , vascular endothelial growth factor , angiogenesis , microcarrier , cell growth , protein kinase b , mapk/erk pathway , chemistry , cancer research , kinase , cell , microbiology and biotechnology , andrology , biology , immunology , apoptosis , vegf receptors , medicine , biochemistry
Resistance of transplanted mesenchymal stem cells ( MSC s) in post‐ischemic heart is limited by their poor vitality. Vascular‐endothelial‐growth‐factor‐A ( VEGF ‐A) as such or slowly released by fibronectin‐coated pharmacologically‐active‐microcarriers ( FN ‐ PAM ‐ VEGF ) could differently affect survival kinases and anti‐apoptotic mediator ( e.g . Bcl‐2). Therefore VEGF ‐A or FN ‐ PAM ‐ VEGF could differently enhance cell proliferation, and/or resistance to hypoxia/reoxygenation (H/R) of MSC s. To test these hypotheses MSC s were incubated for 6‐days with VEGF ‐A alone or with FN ‐ PAM ‐ VEGF . In addition, MSC s pre‐treated for 24‐hrs with VEGF ‐A or FN ‐ PAM ‐ VEGF were subsequently exposed to H/R (72‐hrs 3% O 2 and 3‐hrs of reoxygenation). Cell‐proliferation and post‐hypoxic vitality were determined. Kinases were studied at 30‐min., 1‐ and 3‐days of treatment. Cell‐proliferation increased about twofold ( P < 0.01) 6‐days after VEGF ‐A treatment, but by a lesser extent (55% increase) with FN ‐ PAM ‐ VEGF ( P < 0.05). While MSC pre‐treatment with VEGF ‐A confirmed cell‐proliferation, pre‐treatment with FN ‐ PAM ‐ VEGF protected MSC s against H/R. In the early phase of treatments, VEGF ‐A increased phospho‐Akt, phospho‐ ERK ‐1/2 and phospho‐ PKC ε compared to the untreated cells or FN ‐ PAM ‐ VEGF . Afterword, kinase phosphorylations were higher with VGEF , except for ERK ‐1/2, which was similarly increased by both treatments at 3 days. Only FN ‐ PAM ‐ VEGF significantly increased Bcl‐2 levels. After H/R, lactate dehydrogenase release and cleaved Caspase‐3 levels were mainly reduced by FN ‐ PAM ‐ VEGF . While VEGF ‐A enhances MSC proliferation in normoxia, FN ‐ PAM ‐ VEGF mainly hampers post‐hypoxic MSC death. These different effects underscore the necessity of approaches suited to the various conditions. The use of FN ‐ PAM ‐ VEGF could be considered as a novel approach for enhancing MSC survival and regeneration in hostile environment of post‐ischemic tissues.