title: Characterization and modulation of human mesenchymal stem cell stress pathway response following hypothermic storage.
abstract: Human mesenchymal stem cell (hMSC) research has grown exponentially in the last decade. The ability to process and preserve these cells is vital to their use in stem cell therapy. As such, understanding the complex, molecular-based stress responses associated with biopreservation is necessary to improve outcomes and maintain the unique stem cell properties specific to hMSC. In this study hMSC were exposed to cold storage (4°C) for varying intervals in three different media. The addition of resveratrol or salubrinal was studied to determine if either could improve cell tolerance to cold. A rapid elevation in apoptosis at 1h post-storage as well as increased levels of necrosis through the 24h of recovery was noted in samples. The addition of resveratrol resulted in significant improvements to hMSC survival while the addition of salubrinal revealed a differential response based on the media utilized. Decreases in both apoptosis and necrosis together with decreased cell stress/death signaling protein levels were observed following modulation. Further, ER stress and subsequent unfolded protein response (UPR) stress pathway activation was implicated in response to hMSC hypothermic storage. This study is an important first step in understanding hMSC stress responses to cold exposure and demonstrates the impact of targeted molecular modulation of specific stress pathways on cold tolerance thereby yielding improved outcomes. Continued research is necessary to further elucidate the molecular mechanisms involved in hypothermic-induced hMSC cell death. This study has demonstrated the potential for improving hMSC processing and storage through targeting select cell stress pathways.
authors: CPSI Biotech, 2 Court St, Owego, NY 13827, United States; Institute of Biomedical Technology, Binghamton University, Binghamton, NY 13902, United States. Electronic address: WCorwin@CPSIBiotech.com.
authors: William L
authors: WL
authors: Corwin
authors: CPSI Biotech, 2 Court St, Owego, NY 13827, United States; Institute of Biomedical Technology, Binghamton University, Binghamton, NY 13902, United States.
authors: John M
authors: JM
authors: Baust
authors: Institute of Biomedical Technology, Binghamton University, Binghamton, NY 13902, United States; Department of Biological Sciences, Binghamton University, Binghamton, NY 13902, United States.
authors: John G
authors: JG
authors: Baust
authors: CPSI Biotech, 2 Court St, Owego, NY 13827, United States; Institute of Biomedical Technology, Binghamton University, Binghamton, NY 13902, United States; Department of Biological Sciences, Binghamton University, Binghamton, NY 13902, United States.
authors: Robert G
authors: RG
authors: Van Buskirk
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects*; D002934:Cinnamates / Q000494:pharmacology; D015925:Cryopreservation / Q000379:methods*; D003451:Cryoprotective Agents / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009336:Necrosis; D064587:Osmoregulation; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D013312:Stress, Physiological / Q000187:drug effects*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D002934:Cinnamates; D003451:Cryoprotective Agents; D013267:Stilbenes; C496827:salubrinal; D013890:Thiourea; D000077185:Resveratrol
keywords: Apoptosis; ER stress; Hypothermic storage; Mesenchymal stem cell; Necrosis; Resveratrol; Salubrinal; Unfolded protein response