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A promising treatment option being explored is intradiscal administration of mesenchymal stromal cells (MSCs). However, there remains a gap in knowledge as to whether MSCs from different tissue sources have similar responses to the low pH microenvironment of the IVD and the possible mechanisms governing these responses. To study this, MSCs from three different tissue sources: adipose (adipose\u2010derived mesenchymal stem cell), bone marrow (bone marrow mesenchymal stem cells), and amnion (amniotic membrane mesenchymal stem cell) were cultured at low pHs representative of IVDD. MSCs were assessed for survival, senescence, apoptosis, metabolic activity, and cytokine release profile. Additionally, western blot was utilized to assess acid sensing ion channel 1 and 3 expression. The results of this study indicated that MSC viability, cell proliferation, senescence, and metabolic activity is negatively affected by low pH and alters MSC cytokine production. This study also demonstrated that MSCs behavior is dependent on tissue source. Understanding how MSC behavior is altered by pH will allow further research aimed at increasing the efficacy of MSC therapy to promote in situ IVD\u00a0tissue regeneration to combat IVDD.<\/jats:p>","DOI":"10.1002\/jor.25766","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T23:23:48Z","timestamp":1702423428000},"page":"1303-1313","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mesenchymal stromal cell response to intervertebral disc\u2010like pH is tissue source dependent"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1812-3810","authenticated-orcid":false,"given":"Kyle","family":"Cannon","sequence":"first","affiliation":[{"name":"Laboratory of Orthopaedic Tissue Regeneration and Orthobiologics, Department of Bioengineering Clemson University Clemson South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjitpal","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery The Steadman Clinic Vail Colorado USA"},{"name":"Department Spine &amp; Neck The Steadman Philippon Research Institute Vail Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Laboratory of Orthopaedic Tissue Regeneration and Orthobiologics, Department of Bioengineering Clemson University Clemson South Carolina USA"},{"name":"Department of Bioengineering, Frank H. 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