Amniotic Mesenchymal Stem Cells Enhance Normal Fetal Wound Healing

Abstract

Fetal wound healing involves minimal inflammation and limited scarring. Its mechanisms, which remain to be fully elucidated, hold valuable clues for wound healing modulation and the development of regenerative strategies. We sought to determine whether fetal wound healing includes a hitherto unrecognized cellular component. Two sets of fetal lambs underwent consecutive experiments at midgestation. First, fetuses received an intra-amniotic infusion of labeled autologous amniotic mesenchymal stem cells (aMSCs), in parallel to different surgical manipulations. Subsequently, fetuses underwent creation of 2 symmetrical, size-matched skin wounds, both encased by a titanium chamber. One of the chambers was left open and the other covered with a semipermeable membrane that allowed for passage of water and all molecules, but not any cells. Survivors from both experiments had their wounds analyzed at different time points before term. Labeled aMSCs were documented in all concurrent surgical wounds. Covered wounds showed a significantly slower healing rate than open wounds. Paired comparisons indicated significantly lower elastin levels in covered wounds at the mid time points, with no significant differences in collagen levels. No significant changes in hyaluronic acid levels were detected between the wound types. Immunohistochemistry for substance P was positive in both open and covered wounds. We conclude that fetal wound healing encompasses an autologous yet exogenous cellular component in naturally occurring aMSCs. Although seemingly not absolutely essential to the healing process, amniotic cells expedite wound closure and enhance its extracellular matrix profile. Further scrutiny into translational implications of this finding is warranted.

The Impact of Gestational Age on Targeted Amniotic Cell Profiling in Experimental Neural Tube Defects

“…The mechanisms behind the observed time-dependent fluctuations in the relative proportions of aMSCs and aNSCs in isolated spina bifida in our model are unclear and thus remain purely speculative. It has recently been shown that aMSCs play a central role in fetal wound healing [22]. One could wonder whether the surge in the number of these cells that we observed in the latter portion of gestation could possibly serve a purpose in further protecting the fetus from the trauma associated with imminent delivery.…”

“…On the one hand, aNSCs have been shown to be present in the amniotic fluid in the setting of NTDs, constituting a population of disease-specific amniotic stem cells [21]. On the other, aMSCs are present in the amniotic fluid throughout gestation and have been shown to populate fetal wounds/defects, playing a role in fetal wound healing [22]. …”

Isolation and Characterization of CD271⁺ Stem Cells Derived from Sheep Dermal Skin

“…Despite the use of sheep as a large animal model for a wide range of applications in preclinical research, such as for cartilage tissue engineering [Mrugala et al, 2008], wound healing research [Klein et al, 2011], respiratory disorders [Scheerlinck et al, 2008] and chronic osteochondral defects [Zscharnack et al, 2010], the characterization of ovine MSCs is still limited. This study describes the isolation and characterization of dermal MSCs based on the cell surface marker CD271.…”

Chemokine Involvement in Fetal and Adult Wound Healing

“…79 Furthermore, Roubelakis et al 20 recently reported that platelet-rich plasma promotes regenerative wound healing through recruitment of MSCs. Together these data suggest that there may be a role for circulating stem and progenitor cells in the fetal response that may similarly be, in part, regulated by chemokines.…”