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Generation of vascularized pancreatic progenitors through co-differentiation of endoderm and mesoderm from human pluripotent stem cells.
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- Additional Information
- Source:
Publisher: BioMed Central Country of Publication: England NLM ID: 101527581 Publication Model: Electronic Cited Medium: Internet ISSN: 1757-6512 (Electronic) Linking ISSN: 17576512 NLM ISO Abbreviation: Stem Cell Res Ther Subsets: MEDLINE
- Publication Information:
Original Publication: London : BioMed Central
- Subject Terms:
- Abstract:
Competing Interests: Declarations. Ethical approval and consent to participate: This study does not involve human participants or animals. Use of human pluripotent cell lines (UC and H1) was approved by the ethics committee of Shenzhen Hospital, Beijing University of Chinese Medicine in March 2021 (SZLDH2021LSYA-010). Consent for publication: Not applicable. Artificial intelligence: The authors declare that they have not use AI-generated work in this manuscript. Competing interests: The authors have declared no competing interests.
Background: The simultaneous differentiation of human pluripotent stem cells (hPSCs) into both endodermal and mesodermal lineages is crucial for developing complex, vascularized tissues, yet poses significant challenges. This study explores a method for co-differentiation of mesoderm and endoderm, and their subsequent differentiation into pancreatic progenitors (PP) with endothelial cells (EC).
Methods: Two hPSC lines were utilized. By manipulating WNT signaling, we optimized co-differentiation protocols of mesoderm and endoderm through adjusting the concentrations of CHIR99021 and mTeSR1. Subsequently, mesoderm and endoderm were differentiated into vascularized pancreatic progenitors (vPP) by adding VEGFA. The differentiation characteristics and potential of vPPs were analyzed via transcriptome sequencing and functional assays.
Results: A low-dose CHIR99021 in combination with mTeSR1 yielded approximately 30% mesodermal and 70% endodermal cells. Introduction of VEGFA significantly enhanced EC differentiation without compromising PP formation, increasing the EC proportion to 13.9%. Transcriptomic analyses confirmed the effectiveness of our protocol, showing up-regulation of mesodermal and endothelial markers, alongside enhanced metabolic pathways. Functional assays demonstrated that vPPs could efficiently differentiate into insulin-producing β-cells, as evidenced by increased expression of β-cell markers and insulin secretion.
Conclusion: Our findings provide a robust method for generating vPPs, which holds significant promise for regenerative medicine applications, particularly in diabetes treatment.
(© 2024. The Author(s).)
- References:
Cell Discov. 2024 Apr 30;10(1):45. (PMID: 38684699)
World J Transplant. 2017 Apr 24;7(2):117-128. (PMID: 28507914)
Endocr J. 2014;61(7):647-54. (PMID: 24681780)
Science. 1998 Nov 6;282(5391):1145-7. (PMID: 9804556)
Islets. 2009 Jul-Aug;1(1):2-9. (PMID: 21084843)
Nat Biotechnol. 2014 Nov;32(11):1121-33. (PMID: 25211370)
Cell. 2014 Oct 9;159(2):428-39. (PMID: 25303535)
Nature. 2019 Jan;565(7740):505-510. (PMID: 30651639)
Cell. 2024 Oct 31;187(22):6152-6164.e18. (PMID: 39326417)
Science. 2022 May 13;376(6594):eabl4896. (PMID: 35549404)
J Biomed Sci. 2020 May 22;27(1):67. (PMID: 32443983)
Cell Stem Cell. 2020 Oct 1;27(4):523-531. (PMID: 33007237)
Stem Cell Res Ther. 2023 Aug 30;14(1):223. (PMID: 37649117)
Science. 2020 Nov 13;370(6518):. (PMID: 33184181)
Nat Metab. 2021 Oct;3(10):1372-1384. (PMID: 34650276)
Int J Stem Cells. 2021 Feb 28;14(1):119-126. (PMID: 33377458)
Nat Commun. 2017 Aug 21;8(1):298. (PMID: 28824164)
Cell. 2006 Aug 25;126(4):663-76. (PMID: 16904174)
J Hepatol. 2019 Jun;70(6):1145-1158. (PMID: 30630011)
Stem Cell Reports. 2021 Sep 14;16(9):2395-2409. (PMID: 34450037)
Science. 2001 Oct 19;294(5542):564-7. (PMID: 11577200)
Elife. 2022 Jan 12;11:. (PMID: 35018887)
Development. 2023 Oct 15;150(20):. (PMID: 37883063)
Stem Cell Reports. 2019 Feb 12;12(2):351-365. (PMID: 30661993)
Nat Biotechnol. 2005 Dec;23(12):1534-41. (PMID: 16258519)
Biochemistry (Mosc). 2020 Mar;85(3):264-278. (PMID: 32564731)
Stem Cell Reports. 2020 Jan 14;14(1):138-153. (PMID: 31883919)
Stem Cell Reports. 2022 May 10;17(5):1215-1228. (PMID: 35452596)
Dev Biol. 2010 Nov 1;347(1):216-27. (PMID: 20807526)
Stem Cell Reports. 2023 Nov 14;18(11):2084-2095. (PMID: 37922913)
Cell Regen. 2022 Aug 1;11(1):24. (PMID: 35909206)
Trends Endocrinol Metab. 2010 Aug;21(8):457-63. (PMID: 20359908)
- Grant Information:
JCYJ20220818103407016 Shenzhen Science and Technology Program; SMRF.D2301015 Shenzhen Medical Research Fund; 82172107 National Natural Science Foundation of China; 2024A1515011222 Guangdong Basic and Applied Basic Research Foundation; F-2022-Z99-502266 Special Funds for Strategic Emerging Industry of Shenzhen
- Contributed Indexing:
Keywords: Endoderm differentiation; Human pluripotent stem cells; Mesoderm differentiation; Multi-lineage co-differentiation; Vascularized pancreatic progenitors
- Accession Number:
0 (Chir 99021)
0 (Pyridines)
0 (Vascular Endothelial Growth Factor A)
0 (Pyrimidines)
- Publication Date:
Date Created: 20241224 Date Completed: 20241224 Latest Revision: 20250104
- Publication Date:
20250114
- Accession Number:
PMC11669215
- Accession Number:
10.1186/s13287-024-04120-5
- Accession Number:
39719603
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