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Pleiotropic roles of autophagy in stem cell-based therapies
Nova Southeastern Univ, NSU Cell Therapy Inst, Ft Lauderdale, FL 33314 USA.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Div Cardiothorac Surg & Anesthesiol, Stockholm, Sweden.
Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Div Cardiothorac Surg & Anesthesiol, Stockholm, Sweden.
2019 (English)In: Cytotherapy, ISSN 1465-3249, E-ISSN 1477-2566, Vol. 21, no 4, p. 380-392Article, review/survey (Refereed) Published
Abstract [en]

Stem cells (SCs) have been proven to possess regenerative and immunomodulatory properties and can be used to treat diseases that involve loss of cells due to tissue damage or inflammation. For this approach to succeed, SCs or their derivatives should be able to engraft in the target tissue at least for a short period of time. Unfortunately, once injected, therapeutic SCs will encounter a hostile environment, including hypoxia, lack of nutrients and stromal support, and cells may also be targeted and rejected by the immune system. Therefore, SC's stress-response mechanisms likely play a significant role in survival of injected cells and possibly contribute to their therapeutic efficacy. Autphagy, a stress-response pathway, is involved in many different cellular processes, such as survival during hypoxia and nutrient deprivation, cellular differentiation and de-differentiation, and it can also contribute to their immunovisibility by regulating antigen presentation and cytokine secretion. Autophagy machinery interacts with many proteins and signaling pathways that regulate SC properties, including PI3K/Akt, mammalian target of rapamycin (mTOR), Wnt, Hedgehog and Notch, and it is also involved in regulating intracellular reactive oxygen species (ROS) levels. In this review, we contend that autophagy is an important therapeutic target that can be used to improve the outcome of SC-based tissue repair and regeneration. Further research should reveal whether inhibition or stimulation of autophagy increases the therapeutic utility of SCs and it should also identify appropriate therapeutic regimens that can be applied in the clinic.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD , 2019. Vol. 21, no 4, p. 380-392
National Category
Cell and Molecular Biology Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-383283DOI: 10.1016/j.jcyt.2019.02.007ISI: 000465559700003PubMedID: 30876741OAI: oai:DiVA.org:uu-383283DiVA, id: diva2:1315449
Funder
Swedish Research CouncilAvailable from: 2019-05-14 Created: 2019-05-14 Last updated: 2019-05-14Bibliographically approved

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