Rapid and Robust Derivation of Mesenchymal Stem Cells from Human Pluripotent Stem Cells Via Temporal Induction of Neuralized Ectoderm

Overview

Journal Cell Biosci

Publisher Biomed Central

Specialty Biology

Date 2022 Mar 16

PMID 35292115

Authors

Wei Jin

Yi He

Tuo Li

Fei Long

Xin Qin

Yuan Yuan

Ge Gao

Hosen Md Shakhawat

Xinguang Liu

Guoxiang Jin

Zhongjun Zhou

Affiliations

Soon will be listed here.

Abstract

Background: Mesenchymal stem cells (MSCs) are emerging as the mainstay of regenerative medicine because of their ability to differentiate into multiple cell lineages. The infinite proliferative potential of human pluripotent stem cells (PSCs) grants an unlimited supply of MSCs. Despite their great potential in therapeutic applications, several drawbacks have hindered its clinical translation, including limited number of replication, compromised potential and altered function in late passages. The aim of this study is to establish an efficient method for the production of MSCs from pluripotent stem cells for potential clinical application in rare human disease Hutchinson-Gilford progeria syndrome.

Results: We established a robust method allowing rapid derivation of MSCs from both human iPSCs and ESCs via a temporal induction of neural ectoderm in chemically defined media. The iPSC- and ESC-derived MSCs satisfy the standard criteria of surface markers. They exhibited a high tri-lineage differentiation potential with over 90% transcriptional similarity to the primary MSCs derived from bone marrow. To evaluate the potential application of this method in disease modeling, MSCs were generated from iPSCs derived from a patient with Hutchinson-Gilford progeria syndrome (HGPS-MSCs) and from mutation-rectified HGPS-iPSCs (cHGPS-MSCs). HGPS-MSCs manifested accelerated senescence whereas mutation rectification rescued cellular senescence in HGPS-MSCs.

Conclusions: The robust method of MSC derivation from ESCs and iPSCs provides an efficient approach to rapidly generate sufficient MSCs for in vitro disease modeling and clinical applications.

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References

Gordon L, Rothman F, Lopez-Otin C, Misteli T . Progeria: a paradigm for translational medicine. Cell. 2014; 156(3):400-7. PMC: 6318797. DOI: 10.1016/j.cell.2013.12.028. View

Bernardo M, Fibbe W . Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell. 2013; 13(4):392-402. DOI: 10.1016/j.stem.2013.09.006. View

Liu Q, Spusta S, Mi R, Lassiter R, Stark M, Hoke A . Human neural crest stem cells derived from human ESCs and induced pluripotent stem cells: induction, maintenance, and differentiation into functional schwann cells. Stem Cells Transl Med. 2012; 1(4):266-78. PMC: 3659695. DOI: 10.5966/sctm.2011-0042. View

Srinivasan A, Toh Y . Human Pluripotent Stem Cell-Derived Neural Crest Cells for Tissue Regeneration and Disease Modeling. Front Mol Neurosci. 2019; 12:39. PMC: 6395379. DOI: 10.3389/fnmol.2019.00039. View

Kubben N, Zhang W, Wang L, Voss T, Yang J, Qu J . Repression of the Antioxidant NRF2 Pathway in Premature Aging. Cell. 2016; 165(6):1361-1374. PMC: 4893198. DOI: 10.1016/j.cell.2016.05.017. View

Li W, Huang L, Zeng J, Lin W, Li K, Sun J . Characterization and transplantation of enteric neural crest cells from human induced pluripotent stem cells. Mol Psychiatry. 2016; 23(3):499-508. PMC: 5822467. DOI: 10.1038/mp.2016.191. View

Zhao Q, Gregory C, Lee R, Reger R, Qin L, Hai B . MSCs derived from iPSCs with a modified protocol are tumor-tropic but have much less potential to promote tumors than bone marrow MSCs. Proc Natl Acad Sci U S A. 2014; 112(2):530-5. PMC: 4299223. DOI: 10.1073/pnas.1423008112. View

Wang X, Lazorchak A, Song L, Li E, Zhang Z, Jiang B . Immune modulatory mesenchymal stem cells derived from human embryonic stem cells through a trophoblast-like stage. Stem Cells. 2015; 34(2):380-91. DOI: 10.1002/stem.2242. View

Kotobuki N, Katsube Y, Katou Y, Tadokoro M, Hirose M, Ohgushi H . In vivo survival and osteogenic differentiation of allogeneic rat bone marrow mesenchymal stem cells (MSCs). Cell Transplant. 2008; 17(6):705-12. DOI: 10.3727/096368908786092793. View

10.

Osmanagic-Myers S, Kiss A, Manakanatas C, Hamza O, Sedlmayer F, Szabo P . Endothelial progerin expression causes cardiovascular pathology through an impaired mechanoresponse. J Clin Invest. 2018; 129(2):531-545. PMC: 6355303. DOI: 10.1172/JCI121297. View

11.

Hamczyk M, Villa-Bellosta R, Gonzalo P, Andres-Manzano M, Nogales P, Bentzon J . Vascular Smooth Muscle-Specific Progerin Expression Accelerates Atherosclerosis and Death in a Mouse Model of Hutchinson-Gilford Progeria Syndrome. Circulation. 2018; 138(3):266-282. PMC: 6075893. DOI: 10.1161/CIRCULATIONAHA.117.030856. View

12.

Singer N, Caplan A . Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol. 2010; 6:457-78. DOI: 10.1146/annurev-pathol-011110-130230. View

13.

Squillaro T, Peluso G, Galderisi U . Clinical Trials With Mesenchymal Stem Cells: An Update. Cell Transplant. 2015; 25(5):829-48. DOI: 10.3727/096368915X689622. View

14.

Nissan X, Blondel S, Navarro C, Maury Y, Denis C, Girard M . Unique preservation of neural cells in Hutchinson- Gilford progeria syndrome is due to the expression of the neural-specific miR-9 microRNA. Cell Rep. 2012; 2(1):1-9. DOI: 10.1016/j.celrep.2012.05.015. View

15.

Kyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M, Oreshkova T, Belemezova K . Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells. 2014; 6(5):552-70. PMC: 4178255. DOI: 10.4252/wjsc.v6.i5.552. View

16.

Elahi K, Klein G, Avci-Adali M, Sievert K, MacNeil S, Aicher W . Human Mesenchymal Stromal Cells from Different Sources Diverge in Their Expression of Cell Surface Proteins and Display Distinct Differentiation Patterns. Stem Cells Int. 2016; 2016:5646384. PMC: 4684891. DOI: 10.1155/2016/5646384. View

17.

Jiang X, Gwye Y, McKeown S, Bronner-Fraser M, Lutzko C, Lawlor E . Isolation and characterization of neural crest stem cells derived from in vitro-differentiated human embryonic stem cells. Stem Cells Dev. 2008; 18(7):1059-70. PMC: 4606969. DOI: 10.1089/scd.2008.0362. View

18.

Mitxitorena I, Infante A, Gener B, Rodriguez C . Suitability and limitations of mesenchymal stem cells to elucidate human bone illness. World J Stem Cells. 2019; 11(9):578-593. PMC: 6789184. DOI: 10.4252/wjsc.v11.i9.578. View

19.

Zhang J, Lian Q, Zhu G, Zhou F, Sui L, Tan C . A human iPSC model of Hutchinson Gilford Progeria reveals vascular smooth muscle and mesenchymal stem cell defects. Cell Stem Cell. 2010; 8(1):31-45. DOI: 10.1016/j.stem.2010.12.002. View

20.

Huang X, Sun Z, Miyagi Y, McDonald Kinkaid H, Zhang L, Weisel R . Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation. 2010; 122(23):2419-29. DOI: 10.1161/CIRCULATIONAHA.110.955971. View