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Promotion of Platelet Production by Co-Transplantation of Mesenchymal Stem Cells in Bone Marrow Transplantation

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Therapeutic strategies that can promote platelet production are in demand to enhance clinical outcomes of bone marrow transplantation (BMT). Our research group has studied human tonsil-derived mesenchymal stem cells (T-MSCs) and their effectiveness in promoting bone marrow (BM) engraftment. Here, we analyzed the effects of T-MSCs on platelet production and hemostasis.

Methods:

Donor BM cells (BMCs) were isolated from C57BL/6 mice and transplanted with or without T-MSCs to BALB/c recipient mice. Mice were sacrificed and blood cells were counted using an Auto Hematology Analyzer. Femur sections were stained with CD41 antibody to analyze megakaryocytes in the BM. Growth factor secretion from MSCs was analyzed using the Quantibody Array. Effects of T-MSC conditioned medium (CM) on megakaryopoiesis were investigated using the MegaCult assay. In a mouse model of BMT, T-MSC CM was injected with or without anti-placental growth factor (α-PlGF) blocking antibody, and blood cell numbers and coagulation were analyzed.

Results:

T-MSC co-transplantation increased percent survival of BMT mice. Platelet numbers were significantly lower in the BMC-only group, whereas T-MSC co-transplantation restored circulating platelets to levels similar to those of the control group. Significantly reduced numbers of CD41 + megakaryocytes in Bu-Cy and BMC groups were increased by T-MSC co-transplantation. PlGF secretion from T-MSCs were detected and enhanced megakaryopoiesis, platelet production, and coagulation by T-MCS CM were disrupted in the presence of the α-PlGF blocking antibody.

Conclusion:

We demonstrated the effectiveness of T-MSC co-transplantation in promoting platelet production and coagulation after BMT. These findings highlight the potential therapeutic relevance of T-MSCs for preventing thrombocytopenia after BMT.

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Acknowledgements

This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (Grant Number: HI18C2392), the National Research Foundation of Korea funded by the Ministry of Science and ICT (2020R1C1C1014665) and RP-Grant 2020 of Ewha Womans University.

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Author notes

  1. Yu-Hee Kim and Hyun-Ji Lee have contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology, Ewha Womans University College of Medicine, 25 Magokdong-ro 2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea

    Yu-Hee Kim, Hyun-Ji Lee, Kyung-Ah Cho, Jungwoo Kim & So-Youn Woo

  2. Advanced Biomedical Research Institute, Ewha Womans University Seoul Hospital, 25 Magokdong-ro 2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea

    Yu-Hee Kim

  3. Department of Biochemistry, Ewha Womans University College of Medicine, 25 Magokdong-ro 2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea

    Joo-Won Park

  4. Department of Pediatrics, Ewha Womans University College of Medicine, 25 Magokdong-ro 2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea

    Kyung-Ha Ryu

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  1. Yu-Hee Kim
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Correspondence to Kyung-Ha Ryu.

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The animal studies were performed after receiving approval of the Institutional Animal Care and Use Committee (IACUC) in Ewha Womans University College of Medicine (IACUC approval No. EUM 20–014).

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Kim, YH., Lee, HJ., Cho, KA. et al. Promotion of Platelet Production by Co-Transplantation of Mesenchymal Stem Cells in Bone Marrow Transplantation. Tissue Eng Regen Med 19, 131–139 (2022). https://doi.org/10.1007/s13770-021-00401-9

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