Chimerism as the basis for organ repair

Abstract

Organ and tissue repair are complex processes involving signaling molecules, growth factors, and cell cycle regulators that act in concert to promote cell division and differentiation at sites of injury. In embryonic development, progenitor fetal cells are actively involved in reparative mechanisms and display a biphasic interaction with the mother; and there is constant trafficking of fetal cells into maternal circulation and vice versa. This phenomenon of fetal microchimerism may have significant impact considering the primitive, multilineage nature of these cells. In published work, we have reported that fetal‐derived placental cells expressing the homeodomain protein CDX2 retain all “stem” functional proteins of embryonic stem cells yet are endowed with additional functions in areas of growth, survival, homing, and immune modulation. These cells exhibit multipotency in vitro and in vivo, giving rise to spontaneously beating cardiomyocytes and vascular cells. In mouse models, CDX2 cells from female placentas can be administered intravenously to male mice subjected to myocardial infarction with subsequent homing of the CDX2 cells to infarcted areas and evidence of cellular regeneration with enhanced cardiac function. Elucidating the role of microchimeric fetal‐derived placental cells may have broader scientific potential, as one can envision allogeneic cell therapy strategies targeted at tissue regeneration for a variety of organ systems.

Three-Dimensional Migration of Human Amniotic Fluid Stem Cells Involves Mesenchymal and Amoeboid Modes and is Regulated by mTORC1

“… 77 PAPCs are known to enter the maternal peripheral blood system, distribute, exit the vasculature and infiltrate maternal tissues and organs. 78 , 79 , 80 , 81 , 82 In this respect, the here proven invasion and transendothelial migration capacities of hAFSCs represent the missing pieces to complete this puzzle in support of their suggested role in FCM.…”

“…And finally, it is speculated that fetal microchimerism could simply be a biologically irrelevant, incidental by‐product of pregnancy. 79 , 80 , 81 , 82 However, whereas this pregnancy‐induced trafficking of small amounts of fetal cells to the mother has already intensively been studied, the cellular origin of PAPCs is still under discussion. Already some years ago, we argued that hAFSCs exhibit features, such as nonadhesive proliferation and survival, nontumorigenic behavior and the wide differentiation potential, which support their putative role in FCM.…”

Multipotent fetal stem cells in reproductive biology research

“…These fetal stem cells are considered to play a beneficial role for the mother mainly by their involvement in tissue regeneration. However, negative implications of this deposition of fetal cells in the mother's body for the maternal health have also been discussed [74][75][76]. Although the first description of this phenomenon, designated fetomaternal microchimerism, goes back to the year 1893 [77], the origin of these fetal stem cells in the mother´s body still remains elusive [78,79].…”

Biomaterials‐Based Cell Therapy for Myocardial Tissue Regeneration

“…Recently, a variety of cells have been reported to treat CVDs, including primary CMs, [10,11] cardiac fibroblasts (CFs), [12] cardiosphere-derived cells (CDCs), [13][14][15][16][17] skeletal myoblasts (SkM), [18,19] mesenchymal stem cells (MSCs), [20,21] cardiac stem/progenitor cells (CSCs/CPCs), [22][23][24][25][26] embryonic stem cells (ESCs), [27][28][29][30] induced pluripotent stem cells (iPS), [12,[31][32][33] pluripotent stem cells (PSCs), [34,35] and engineered cells [36][37][38][39][40] (such as genetically engineered HGF-MSCs [41] ). Besides the directly replenish of the lost CMs (injecting with primary CMs or derived CMs), a lot of studies report that cells may influence myocardial regeneration in a paracrine manner, [42] thereby improving ventricular ejection function and exercise capacity, [14,17,[43][44][45] reducing fibrotic area and wall thickness, [15,43,46] and increasing the level of vascularization. [26,…”