Yu-Hee Kim1,2, Hyun-Ji Lee1, Kyung-Ah Cho1, Jungwoo Kim1, Joo-Won Park3, So-Youn Woo1, Kyung-Ha Ryu4. 1. Department of Microbiology, Ewha Womans University College of Medicine, 25 Magokdong-ro 2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea. 2. Advanced Biomedical Research Institute, Ewha Womans University Seoul Hospital, 25 Magokdong-ro 2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea. 3. Department of Biochemistry, Ewha Womans University College of Medicine, 25 Magokdong-ro 2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea. 4. Department of Pediatrics, Ewha Womans University College of Medicine, 25 Magokdong-ro 2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea. ykh@ewha.ac.kr.
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.
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.
Authors: Charles A Schiffer; Kari Bohlke; Meghan Delaney; Heather Hume; Anthony J Magdalinski; Jeffrey J McCullough; James L Omel; John M Rainey; Paolo Rebulla; Scott D Rowley; Michael B Troner; Kenneth C Anderson Journal: J Clin Oncol Date: 2017-11-28 Impact factor: 44.544
Authors: Carmelo Carlo-Stella; Massimo Di Nicola; Paolo Longoni; Loredana Cleris; Cristiana Lavazza; Raffaella Milani; Marco Milanesi; Michele Magni; Virgilio Pace; Francesco Colotta; Maria A Avanzini; Franca Formelli; Alessandro M Gianni Journal: Stem Cells Date: 2006-09-28 Impact factor: 6.277
Authors: Lise J Estcourt; Michael Desborough; Susan J Brunskill; Carolyn Doree; Sally Hopewell; Michael F Murphy; Simon J Stanworth Journal: Cochrane Database Syst Rev Date: 2016-03-15