Mouse Pluripotent Stem Cell Differentiation Under Physiological Oxygen Reduces Residual Teratomas
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Introduction Residual pluripotent stem cells (PSC) within differentiated populations are problematic because of their potential to form tumors. Simple methods to reduce their occurrence are needed. Methods Here, we demonstrate that control of the oxygen partial pressure (pO 2) to physiological levels typical of the developing embryo, enabled by culture on a highly oxygen permeable substrate, reduces the fraction of PSC within and the tumorigenic potential of differentiated populations. Results Differentiation and/or extended culture at low pO 2 reduced measured pluripotency markers by up to four orders of magnitude for mouse PSCs (mPSCs). Combination with cell sorting increased the reduction to as much as six orders of magnitude. Upon implantation into immunocompromised mice, mPSCs differentiated at low pO 2 either did not form tumors or formed tumors at a slower rate than at high pO 2. Conclusions Low pO 2 culture alone or in combination with other methods is a potentially straightforward method that could be applied to future cell therapy protocols to minimize the possibility of tumor formation.
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Highly proliferative uncommitted progenitors or residual hPSCs in the final SC-islet product have the potential to form tumors.
“Of greatest concern is the potential for highly proliferative uncommitted progenitors or residual hPSCs to be present in the final SC-islet product that have the potential to form tumors.158–160”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [158]
The Introduction (page unavailable) says residual pluripotent stem cells can persist after differentiation and cause tumors upon implantation. The Discussion (page unavailable) reports tumor formation after transplantation of differentiated mouse stem-cell populations. The paper does not establish tumor risk from highly proliferative uncommitted progenitors or specifically examine a final human SC-islet product. (LLM, conf=0.85)
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Self-citation
- Authors
- Millman, J. R., Tan, J. H., & Colton, C. K.
- Affiliations
- Washington University in St. Louis (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Millman, Jeffrey R.
- Colton, Clark K.
- ORCID
- Millman, Jeffrey R.
- Venue
- Cellular and Molecular Bioengineering
- Published
- 2021-07-12
- Volume
- 14
- Issue
- 6
- Pages
- 555-567
- ISSN
- 1865-5025 (ISSN-L)
- 1865-5033
- PMC
- PMC8630352
- OpenAlex
- W3180177814
- Cited by
- 7
- References
- 34
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 2
- FWCI
- 0.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cellular and Molecular Bioengineering (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Funders
- Juvenile Diabetes Research Foundation United States of America (41-2009-803)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- teratoma formation, oxygen partial pressure, low oxygen culture, tumorigenicity, stem cell markers, cell sorting, cell therapy safety
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