In vitro and In vivo Studies on Mesenchymal Stem Cells for Ischemic Stroke Therapy: A Scoping Review of The Therapeutic Effect

Ratih Rinendyaputri,1,2 Ita Margaretha Nainggolan,3 Hasta Handayani Idrus,1 Rachmawati Noverina,4 Wireni Ayuningtyas,4 Fathul Huda,5 Ahmad Faried6 1Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency, Bogor, West Java, Indonesia; 2Doctoral Program, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, 40161, Indonesia; 3Eijkman Research Center for Molecular Biology, Research Organization for Health, National Research and Innovation Agency, Bogor, West Java, Indonesia; 4Bio Farma Stem Cell Research and Development, Bandung, West Java, 40161, Indonesia; 5Department of Neurology, Faculty of Medicine, Dr Hasan Sadikin Central General Hospital/Universitas Padjadjaran, Bandung, West Java, 40161, Indonesia; 6Neurosurgery Department, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, 40161, IndonesiaCorrespondence: Ahmad Faried, Email [email protected]: Mesenchymal stem cells (MSCs) have a paracrine impact and may regenerate a variety of tissues. This represents a new prospect in cell-based stroke treatment. Several in vitro and in vivo investigations have demonstrated the neuroprotective and neurogenesis properties of MSCs and their secretome.Purpose: This review provides a comprehensive analysis of the therapeutic effects of MSCs and their secretome on stroke models in vitro and in vivo.Methods: A coverage evaluation is undertaken in accordance with PRISMA-ScR principles. The selection procedure includes the identification of items. Scopus site, PubMed and ScienceDirect, are used for in vitro and in vitro research, including electronic searches. The search terms include “ischemic stroke” or “MCAO”, “MSC”, “secretome”, and “neurogenesis” or “angiogenesis”. The searches are limited to English-language articles with full text availability.Results: After selecting 390 papers from two search engines, 94 publications satisfied the review criteria for using MSCs and secretomes for ischemic stroke treatment. We comprehensively review both in vitro and in vivo studies, analyzing aspects such as the source and treatment of MSCs and secretomes, as well as administration, dosage, and mechanisms of therapeutic effects in stroke models.Conclusion: MSC and secretome therapy for stroke have shown promising results in both in vitro and in vivo models. Exploration of alternative MSC sources, refining of isolation techniques, transfection of various proteins, and combination with herbal medicine are all efforts to improve the preclinical model. This work can be used as a reference for preclinical researchers to help with research design and translational research in clinical trials.Keywords: middle cerebral artery occlusion (MCAO), conditioned medium/CM, secretome, mesenchymal stem cells (MSC), stroke ischemic