Factors Secreted by Mesenchymal Stem Cells and Endothelial Progenitor Cells Have Complementary Effects on Angiogenesis In Vitro

Abstract

Stem cell-based therapy for myocardial regeneration has reported several functional improvements that are attributed mostly to the paracrine effects stimulating angiogenesis and cell survival. This study was conducted to comparatively evaluate the potential of factors secreted by mesenchymal stem cells (MSCs) in normoxic and hypoxic conditions to promote tissue repair by sustaining endothelial cell (EC) adhesion and proliferation and conferring protection against apoptosis. To this aim, a conditioned medium (CM) was generated from MSCs after 24-h incubation in a serum-free normal or hypoxic environment. MSCs exhibited resistance to hypoxia, which induced increased secretion of vascular endothelial growth factor (VEGF) and decreased levels of other cytokines, including stromal-derived factor-1 (SDF). The CM derived from normal (nMSC-CM) and hypoxic cells (hypMSC-CM) induced similar protective effects on H9c2 cells in hypoxia. Minor differences were noticed in the potential of normal versus hypoxic CM to promote angiogenesis, which were likely connected to SDFa and VEGF levels: the nMSC-CM was more effective in stimulating EC migration, whereas the hypMSC-CM had an enhanced effect on EC adhesion. However, the factors secreted by MSCs in normoxic or hypoxic conditions supported adhesion, but not proliferation, of ECs in vitro, as revealed by impedance-based dynamic assessments. Surprisingly, factors secreted by other stem/progenitor cells, such as endothelial progenitor cells (EPCs), had complementary effects to the MSC-CM. Thus, the EPC-CM, in either a normal or hypoxic environment, supported EC proliferation, but did not sustain EC adhesion. Combined use of the MSC-CM and EPC-CM promoted both EC adhesion and proliferation, suggesting that the local angiogenesis at the site of ischemic injury might be better stimulated by simultaneous releasing of factors secreted by multiple stem/progenitor cell populations.

Bone Marrow-Derived Endothelial Progenitor Cells Protect Postischemic Axons after Traumatic Brain Injury

“…These include but are not limited to vascular endothelial growth factor, stromal cell-derived factor 1a (SDF-1a), basic fibroblast growth factor, brain-derived neurotrophic factor. 25,30,31 Our data indicate that EPCs can be exploited to provide survival cues to axons after ischemic but not mechanical injury. One reason for this difference in response may be related to the severity of injury incurred through mechanical trauma in relation to ischemic injury.…”

Hypoxic and ischemic effects on gene and protein expression levels of paracrine factors by human olfactory mucosa mesenchymal-like stem cells

“…[9][10][11] There is only 3%-14% oxygen in brain. 12 Hypoxia 13 can affect the secretion of paracrine factors, 14 alter gene expression of MSCs 15,16 and enhance proliferation of MSCs. [17][18][19][20][21] The amount of serum present in the culture media also affects stem cell behavior.…”

“…14,15,32 Hypoxia caused an increase in the secretion of transforming growth factor-β2; insulin-like growth factor (IGF) binding proteins 2, 3, 4 and 6; IGF-II and interleukin-7, 33,34 and reduced the secretion of stromal cell derived factor-1, macrophage colony stimulating factor, interleukin-1 receptor antagonist, RANTES, chemokine (C-X-C motif) ligand 1, lactate dehydrogenase and chemokine (C-X-C motif) ligand 10 by MSCs. 16,35 In short, hypoxia changes the paracrine secretions of MSCs, which would have implications for the role they play in reducing the loss of function in the brain after cerebral ischemia. Exposure to a hypoxic environment leads to obvious changes in cellular physiology.…”

Evaluating Effect of Mesenchymal Stem Cells on Expression of TLR2 and TLR4 in Mouse DCs

“…32 MSCs in in vitro condition express a small amount of MHC I and are negative for MHC II, CD40, and CD86 and, therefore, is unable to stimulate immune reaction in the host. 33 It has been documented that MSCs play their immunomodulatory functions via cell contact or secretion of certain factors. 34 Previous investigations demonstrated that DCs are the most cells which are under immunomodulatory functions of MSCs.…”