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Therapeutic Effects of Mesenchymal Stem Cells Derived From Bone Marrow, Umbilical Cord Blood, and Pluripotent Stem Cells in a Mouse Model of Chemically Induced Inflammatory Bowel Disease

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Abstract

Acute inflammatory bowel disease (AIBD) is a wide clinical entity including severe gastrointestinal pathologies with common histopathological basis. Epidemiologically increasing diseases, such as necrotizing enterocolitis (NEC), gastrointestinal graft versus host disease (GVHD), and the primary acute phase of chronic inflammatory bowel disease (CIBD), exhibit a high necessity for new therapeutic strategies. Mesenchymal stem cell (MSC) cellular therapy represents a promising option for the treatment of these diseases. In our study, we comparatively assess the efficacy of human MSCs derived from bone marrow (BM), umbilical cord blood (UCB), human embryonic stem cells (ESCs), or human-induced pluripotent stem cells (iPSCs) in a mouse model of chemically induced acute enterocolitis. The laboratory animals were provided ad libitum potable dextrane sulfate sodium solution (DSS) in order to reproduce an AIBD model and then individually exposed intraperitoneally to MSCs derived from BM (BM-MSCs), UCB (UCB-MSCs), ESCs (ESC-MSCs), or iPSCs (iPSC-MSCs). The parameters used to evaluate the cellular treatment efficacy were the animal survival prolongation and the histopathological-macroscopic picture of bowel sections. Although all categories of mesenchymal stem cells led to statistically significant survival prolongation compared to the control group, significant clinical and histopathological improvement was observed only in mice receiving BM-MSCs and UCB-MSCs. Our results demonstrated that the in vivo anti-inflammatory effect of ESC-MSCs and iPSC-MSCs was inferior to that of UCB-MSCs and BM-MSCs. Further investigation will clarify the potential of ESCs and iPSC-derived MSCs in AIBD treatment.

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Acknowledgments

G.E., T.M., K.E.: conception and design, provision of study material manuscript writing, final approval of manuscript, scientific guidance K.A, V.I., S.I., M.A.: mesenchymal stem cell derivation P.E.: provision of experimental surgery structures and animal model design, D.E.: histopathological evaluation and over all special contribution to my father Kagias Dimitrios for his continuous support.

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Authors and Affiliations

  1. Obstetric and Gynecological Department, General Hospital of Athens “Konstantopouleio”, Nea Ionia, Greece

    Argyro Kagia

  2. Faculty of Medicine, Department of Genetics, Medical School, National & Kapodistrian University of Athens, Athens, Greece

    Maria Tzetis & Emmanuel Kanavakis

  3. Aghia Sophia Children’s Hospital, Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Athens, Greece

    Emmanuel Kanavakis

  4. Laboratory of Experimental Surgery and Surgical Research “Christeas Hall”, Medical School, National & Kapodistrian University of Athens, Athens, Greece

    Despina Perrea

  5. Stem Cell Transplant Unit, Aghia Sophia Children’s Hospital of Athens, Athens, Greece

    Irene Sfougataki, Anny Mertzanian, Ioanna Varela, Angeliki Karagiannidou & Evgenios Goussetis

  6. Histopathological Department, “Helena Venizelou” Gynecological Hospital, Athens, Greece

    Aikaterini Dimopoulou

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  1. Argyro Kagia
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Correspondence to Argyro Kagia.

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The animal experiments were conducted under protocols reviewed and approved by Institutional Animal Care and Use Committee (Athens, Protocol Number K/5449). All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.

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Kagia, A., Tzetis, M., Kanavakis, E. et al. Therapeutic Effects of Mesenchymal Stem Cells Derived From Bone Marrow, Umbilical Cord Blood, and Pluripotent Stem Cells in a Mouse Model of Chemically Induced Inflammatory Bowel Disease. Inflammation 42, 1730–1740 (2019). https://doi.org/10.1007/s10753-019-01033-x

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