Injectable and Cryopreservable MSC-Loaded PLGA Microspheres for Recovery from Chemically Induced Liver Damage
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Article www.springer.com/13233 pISSN 1598-5032 eISSN 2092-7673
Injectable and Cryopreservable MSC-Loaded PLGA Microspheres for Recovery from Chemically Induced Liver Damage Min-Jeong Park1,2 Misook Choi3 Mina Kim3 Don-Haeng Lee*,1,3
1
Department of New Drug Development, College of Medicine, Inha University, Incheon 22332, Korea Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea 3 Utah-Inha DDS & Advanced Therapeutics Research Center, Incheon 22212, Korea 2
Received March 24, 2020 / Revised June 19, 2020 / Accepted June 29, 2020 Abstract: Biodegradable porous microspheres, which were initially used as supports for cell growth, are known to have the advantages of maintaining a differentiated cell phenotype and allowing for cell expansion owing to their large surface area. The use of porous microspheres ensures good retention of engrafted cells as platforms for cell delivery. In this study, injectable and porous poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were fabricated using a microfluidic system. These microspheres had a relatively uniform size and a porous and interconnected internal structure. The prepared PLGA microspheres were used as stem cell carriers for therapy. Here, we demonstrated the feasibility of mesenchymal stem cell (MSC)-loaded microspheres as cell therapy agents for liver damage. The results obtained from a chemically induced liver damage model showed that MSC-loaded microspheres effectively promoted liver recovery. These findings clearly show the feasibility of using injectable microspheres for the therapy and regeneration of tissues. Keywords: porous microsphere, PLGA, cell delivery, liver damage, mesenchymal stem cells.
1. Introduction Numerous research groups have proved the potential of cell transplantation in tissue regeneration by directly injecting cells into the defect or disease site.1-4 For example, myocardial injections loaded with mesenchymal stem cells (MSCs) have been used to treat heart diseases such as angina or myocardial infarction.5-7 In vitro MSCs have the potential to differentiate into hepatocytes.8,9 In addition, studies from other groups have demonstrated that rat or human MSCs can differentiate into hepatocyte-like cells after transplantation into rat liver.10-12 Recently, studies have reported that transplantation of rat bone marrow MSCs protects rat livers from chemically induced liver fibrosis.13,14 Although cell transplantation has been demonstrated to improve liver function after injury, poor graft retention after cell delivery has limited application to treatment. Through the needle holes created during cell transplantation, a significant portion of the cells leak or enter the systemic circulation.15,16 The precise control of the amount, distribution, and viability of injected cells has become a major challenge in maximizing therapeutic effects for bone defects or retinal degenerations and elucidating the healing mechanism.17,18 Hydrogels obtained by cross-linking natural or synthetic polymers were inj
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