Amniotic Membrane MSCs Support the Robust Expansion of Cord Blood HSCs

Review of “Human amniotic mesenchymal stromal cells support the ex vivo expansion of cord blood hematopoietic stem cells” from STEM CELLS Translational Medicine by Stuart P. Atkinson

The placenta supports hematopoiesis during fetal development; therefore, this organ may possess certain characteristics pertaining to the hematopoietic niche [1, 2]. Mesenchymal stem cells (MSCs) derived from the amniotic membrane of the human term placenta (AMSCs) possess potent immunomodulatory activity [3, 4] and can trigger regeneration in animal models of a range of disease and disorders, including liver [5] and lung fibrosis [6] (See the STEM CELLS Translational Medicine article for more!), traumatic brain injury [7], and cardiac ischemia [8]. The therapeutic effect of AMSCs in the absence of long-term engraftment suggests that their therapeutic potential derives from paracrine acting factors [3, 4].

A STEM CELLS Translational Medicine article from researchers led by Ornella Parolini (Università Cattolica del Sacro Cuore, Rome, Italy) now reports on the exploration of human AMSCs as an adequate alternative to bone marrow-derived (BM-) MSCs as a feeder layer supporting the ex vivo expansion of cord blood hematopoietic stem cells (HSCs) for transplantation purposes [9].

Orticelli et al. first established broad immunophenotypic similarities between BM-MSCs and AMSCs, suggesting that these placental cells may represent an interesting alternative for HSC expansion. A subsequent comparison of HSCs cultured with a BM-MSC feeder layer to HSCs cocultured directly on AMSCs or indirectly cocultured using transwell culture, which allows secreted factors to pass between cells without allowing direct cell-to-cell contact, provided evidence that both coculture set-ups supported the ex vivo expansion of HSCs.

AMSCs supported the expansion of primitive HSCs subsets (long-term and short-term reconstituting HSCs), primitive hematopoietic progenitor subsets (HSCs/multipotent progenitors, lymphoid-primed multipotent progenitors, and multilymphoid progenitors), and committed hematopoietic progenitor lineages (common myeloid progenitors, megakaryocyte/erythrocyte progenitors, and granulocyte-monocyte progenitors) in a manner equal to or better than BM-MSCs. Overall, AMSCs specifically favored the expansion of short-term reconstituting HSCs, common myeloid progenitors, and granulocyte-monocyte progenitors.

Coculture with AMSCs also maintained the clonogenic ability of hematopoietic progenitors in a comparable manner to BM-MSCs, supporting the generation of granulocyte, erythrocyte, macrophage, and megakaryocyte colony-forming units. Finally, and perhaps most importantly, AMSCs also supported the expansion and maintenance of long-term culture-initiating cells, which possess HSC-niche repopulating activity.

Overall, this detailed comparison supports human AMSCs as an exciting and easy-to-source alternative to BM-MSCs regarding the expansion of cord blood-derived HSCs. Can AMSCs now allow for the efficient expansion of cord blood-derived HSCs to generate the enormous numbers of cells required for various therapeutic applications?

For more on how amniotic membrane-derived MSCs may provide a boost to HSC transplantation-based therapies, stay tuned to the Stem Cells Portal!

References

1. Alvarez-Silva M, Belo-Diabangouaya P, Salaün J, et al., Mouse placenta is a major hematopoietic organ. Development 2003;130:5437-5444.
2. Gekas C, Dieterlen-Lièvre F, Orkin SH, et al., The Placenta Is a Niche for Hematopoietic Stem Cells. Developmental Cell 2005;8:365-375.
3. Antonietta S, Ornella P, Berthold H, et al., Soluble Factors of Amnion-Derived Cells in Treatment of Inflammatory and Fibrotic Pathologies. Current Stem Cell Research & Therapy 2013;8:6-14.
4. Silini AR, Magatti M, Cargnoni A, et al., Is Immune Modulation the Mechanism Underlying the Beneficial Effects of Amniotic Cells and Their Derivatives in Regenerative Medicine? Cell Transplantation 2017;26:531-539.
5. Kubo K, Ohnishi S, Hosono H, et al., Human Amnion-Derived Mesenchymal Stem Cell Transplantation Ameliorates Liver Fibrosis in Rats. Transplantation Direct 2015;1.
6. Cargnoni A, Romele P, Bonassi Signoroni P, et al., Amniotic MSCs reduce pulmonary fibrosis by hampering lung B-cell recruitment, retention, and maturation. STEM CELLS Translational Medicine 2020;9:1023-1035.
7. Pischiutta F, Brunelli L, Romele P, et al., Protection of Brain Injury by Amniotic Mesenchymal Stromal Cell-Secreted Metabolites. Critical Care Medicine 2016;44.
8. Tsuji H, Miyoshi S, Ikegami Y, et al., Xenografted Human Amniotic Membrane–Derived Mesenchymal Stem Cells Are Immunologically Tolerated and Transdifferentiated Into Cardiomyocytes. Circulation Research 2010;106:1613-1623.
9. Orticelli V, Papait A, Vertua E, et al., Human amniotic mesenchymal stromal cells support the ex vivo expansion of cord blood hematopoietic stem cells. STEM CELLS Translational Medicine 2021;10:1516-1529.