Abstract
Stem cell function is thought to be tightly regulated by growth factor concentration in the confines of the microenvironmental niche. Therefore, the response of human mesenchymal stem cells (hMSCs) was studied in culture with mechano-growth factor (MGF), an isoform of IGF-1 known to be expressed in the heart following injury. Chemotactic migration of hMSCs increased in response to a peptide analog corresponding to the E-domain region of the MGF prohormone, which was greater than the IGF-1 polypeptide after 20 h of culture. Compared to control without growth factor, migration was significantly less with a scrambled peptide ( p = 0.025) or a peptide harboring a serine to alanine substitution near the carboxy end ( p = 0.002). The IGF-1 polypeptide increased proliferation of small (5–9 μm) but not large (> 13 μm) hMSCs, whereas the E-domain peptide (MGF-E) had no effect on proliferation. Thus, there are complex biological responses of hMSCs to the prehormone of IGF with respect to migration and proliferation. Since neonatal myocytes but not hMSCs express MGF when strained cyclically at 20%, overloading of the heart may trigger immigration of stem cells. It seems possible that regions of the IGF prohormone may act differentially, or in a combinatorial manner, to benefit cardiac tissue recovery after injury.
Highlights
Mesenchymal stem cells (MSCs) are advantageous for tissue regeneration because of availability, self-renewal and differentiation into multiple cell types [1]
HMSCs isolated from bone marrow aspirates were cultured in complete culture media (CCM) consisting of MEM-α supplemented with 16.5% FBS, 2 mM L-glutamine, 100 units/mL penicillin and 100 μg/mL streptomycin. human mesenchymal stem cells (hMSCs) were obtained from the Tulane University Center for Gene Therapy or AllCells (Berkeley, CA)
There was higher variability across 3 human donors, mechano-growth factor (MGF)-E (LD) caused significantly more migration compared to MGF-E (S-A) (p≤0.006) with a trend for increase versus SCR (p=0.06) (Figure 1D)
Summary
Mesenchymal stem cells (MSCs) are advantageous for tissue regeneration because of availability, self-renewal and differentiation into multiple cell types [1]. Growth factors might enhance clinical outcomes via proliferation and directed migration. Members of the insulin-like growth factor (IGF) family mediate several regenerative processes, including modulation of inflammatory responses, apoptosis and proliferation. Final cleavage yields identical mature peptides but with different E-domains [5], one of which is preferentially expressed in damaged skeletal muscle [6] and found in heart and other tissues [7]. In humans, this isoform is named IGF-1Ec or mechano-growth factor (MGF), Figure 1A
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