Ex vivo Induction of Apoptotic Mesenchymal Stem Cell by High Hydrostatic Pressure
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Ex vivo Induction of Apoptotic Mesenchymal Stem Cell by High Hydrostatic Pressure Tien Minh Le 1,2 & Naoki Morimoto 3 & Nhung Thi My Ly 4 & Toshihito Mitsui 1 & Sharon Claudia Notodihardjo 1 & Shuichi Ogino 3 & Jun Arata 3 & Natsuko Kakudo 1 & Kenji Kusumoto 1 Accepted: 26 October 2020 # The Author(s) 2020
Abstract Among promising solutions for tissue repair and wound healing, mesenchymal stem (or stromal) cells (MSCs) have been a focus of attention and have become the most clinically studied experimental cell therapy. Recent studies reported the importance of apoptosis in MSC-mediated immunomodulation, in which apoptotic MSCs (apoMSCs) were shown to be superior to living MSCs. Nowadays, high hydrostatic pressure (HHP), a physical technique that uses only fluid pressure, has been developed and applied in various bioscience fields, including biotechnology, biomaterials, and regenerative medicine, as its safe and simply operation. In the current study, we investigated the impact of HHP treatment on human bone marrow-MSC survival and proliferation. Based on the detection of executioner caspase activation, phosphatidylserine exposure, DNA fragmentation (TUNEL) and irrefutable ultrastructural morphological changes on transmission electron microscopy (TEM), our data revealed that HHP treatment induced complete apoptosis in MSCs. Notably, this technique might provide manipulated products for use in cell-based therapies as manufacturing capability expands. We hope that our findings will contribute to the improvement of MSCs or EVs in translational research development. Keywords Apoptosis . Extracellular vesicles . Mesenchymal stem cell (MSC) . High hydrostatic pressure (HHP) . Tissue engineering
Introduction Mesenchymal stem/stroma cells (MSCs, a term first coined by Caplan) are nonhematopoietic stem cells derived from bone marrow [1] that have multipotent differentiation capacity to mesodermal tissues, such as bone, tendon, cartilage, muscle, and fat [2]. This finding was expected to open the era of replacing or repairing damaged tissues of mesenchymal origin. Since then,
* Naoki Morimoto [email protected] 1
Department of Plastic and Reconstructive Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan
2
Department of Orthopaedics, SAIGON International Trauma Orthopaedics (SAIGON - ITO) Hospital, 140C Nguyen Trong Tuyen, Phu Nhuan District, Ho Chi Minh City 72217, Vietnam
3
Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
4
Department of Dermatology, Kansai Medical University, 2-5-1 Shin-machi, 573-1010 Hirakata, Osaka, Japan
MSCs have been a focus of attention for their broad-ranging clinical potential, particularly in the rapidly growing field of regenerative medicine. Over the past decade, numerous advances have been made in the development of MSCs as a therapy for a highly diverse group of diseases, including cardiac, neural, and orthopedic diseases. However, the
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