A Cutting-edge Strategy for Spinal Cord Injury Treatment: Resident Cellular Transdifferentiation

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2023 Sep 15

PMID 37711511

Authors

Yu-Ming Fang

Wei-Can Chen

Wan-Jing Zheng

Yu-Shen Yang

Yan Zhang

Xin-Li Chen

Meng-Qin Pei

Shu Lin

He-Fan He

Affiliations

Soon will be listed here.

Abstract

Spinal cord injury causes varying degrees of motor and sensory function loss. However, there are no effective treatments for spinal cord repair following an injury. Moreover, significant preclinical advances in bioengineering and regenerative medicine have not yet been translated into effective clinical therapies. The spinal cord's poor regenerative capacity makes repairing damaged and lost neurons a critical treatment step. Reprogramming-based neuronal transdifferentiation has recently shown great potential in repair and plasticity, as it can convert mature somatic cells into functional neurons for spinal cord injury repair and , effectively halting the progression of spinal cord injury and promoting functional improvement. However, the mechanisms of the neuronal transdifferentiation and the induced neuronal subtypes are not yet well understood. This review analyzes the mechanisms of resident cellular transdifferentiation based on a review of the relevant recent literature, describes different molecular approaches to obtain different neuronal subtypes, discusses the current challenges and improvement methods, and provides new ideas for exploring therapeutic approaches for spinal cord injury.

References

Rivetti di Val Cervo P, Romanov R, Spigolon G, Masini D, Martin-Montanez E, Toledo E . Induction of functional dopamine neurons from human astrocytes in vitro and mouse astrocytes in a Parkinson's disease model. Nat Biotechnol. 2017; 35(5):444-452. DOI: 10.1038/nbt.3835. View

Nishimura S, Yasuda A, Iwai H, Takano M, Kobayashi Y, Nori S . Time-dependent changes in the microenvironment of injured spinal cord affects the therapeutic potential of neural stem cell transplantation for spinal cord injury. Mol Brain. 2013; 6:3. PMC: 3556141. DOI: 10.1186/1756-6606-6-3. View

Aydin B, Kakumanu A, Rossillo M, Moreno-Estelles M, Garipler G, Ringstad N . Proneural factors Ascl1 and Neurog2 contribute to neuronal subtype identities by establishing distinct chromatin landscapes. Nat Neurosci. 2019; 22(6):897-908. PMC: 6556771. DOI: 10.1038/s41593-019-0399-y. View

Yoo A, Sun A, Li L, Shcheglovitov A, Portmann T, Li Y . MicroRNA-mediated conversion of human fibroblasts to neurons. Nature. 2011; 476(7359):228-31. PMC: 3348862. DOI: 10.1038/nature10323. View

Kim J, Efe J, Zhu S, Talantova M, Yuan X, Wang S . Direct reprogramming of mouse fibroblasts to neural progenitors. Proc Natl Acad Sci U S A. 2011; 108(19):7838-43. PMC: 3093517. DOI: 10.1073/pnas.1103113108. View

Chen W, Zheng Q, Huang Q, Ma S, Li M . Repressing PTBP1 fails to convert reactive astrocytes to dopaminergic neurons in a 6-hydroxydopamine mouse model of Parkinson's disease. Elife. 2022; 11. PMC: 9208759. DOI: 10.7554/eLife.75636. View

Liu M, Zang T, Zhang C . Direct Lineage Reprogramming Reveals Disease-Specific Phenotypes of Motor Neurons from Human ALS Patients. Cell Rep. 2016; 14(1):115-128. PMC: 4706770. DOI: 10.1016/j.celrep.2015.12.018. View

Wu T, Pinto H, Kamikawa Y, Donohoe M . The BET family member BRD4 interacts with OCT4 and regulates pluripotency gene expression. Stem Cell Reports. 2015; 4(3):390-403. PMC: 4375790. DOI: 10.1016/j.stemcr.2015.01.012. View

Xi G, Hu P, Qu C, Qiu S, Tong C, Ying Q . Induced neural stem cells generated from rat fibroblasts. Genomics Proteomics Bioinformatics. 2013; 11(5):312-9. PMC: 3908478. DOI: 10.1016/j.gpb.2013.09.003. View

10.

Cates K, McCoy M, Kwon J, Liu Y, Abernathy D, Zhang B . Deconstructing Stepwise Fate Conversion of Human Fibroblasts to Neurons by MicroRNAs. Cell Stem Cell. 2020; 28(1):127-140.e9. PMC: 7796891. DOI: 10.1016/j.stem.2020.08.015. View

11.

Grande A, Sumiyoshi K, Lopez-Juarez A, Howard J, Sakthivel B, Aronow B . Environmental impact on direct neuronal reprogramming in vivo in the adult brain. Nat Commun. 2013; 4:2373. PMC: 3786770. DOI: 10.1038/ncomms3373. View

12.

Raposo A, Vasconcelos F, Drechsel D, Marie C, Johnston C, Dolle D . Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis. Cell Rep. 2015; 10(9):1544-1556. PMC: 5383937. DOI: 10.1016/j.celrep.2015.02.025. View

13.

Federation A, Bradner J, Meissner A . The use of small molecules in somatic-cell reprogramming. Trends Cell Biol. 2013; 24(3):179-87. PMC: 3943685. DOI: 10.1016/j.tcb.2013.09.011. View

14.

Chavez A, Scheiman J, Vora S, Pruitt B, Tuttle M, Iyer E . Highly efficient Cas9-mediated transcriptional programming. Nat Methods. 2015; 12(4):326-8. PMC: 4393883. DOI: 10.1038/nmeth.3312. View

15.

Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S, Lipton S . Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell. 2011; 9(2):113-8. PMC: 4567246. DOI: 10.1016/j.stem.2011.07.002. View

16.

Ladewig J, Mertens J, Kesavan J, Doerr J, Poppe D, Glaue F . Small molecules enable highly efficient neuronal conversion of human fibroblasts. Nat Methods. 2012; 9(6):575-8. DOI: 10.1038/nmeth.1972. View

17.

Theodore N, Hlubek R, Danielson J, Neff K, Vaickus L, Ulich T . First Human Implantation of a Bioresorbable Polymer Scaffold for Acute Traumatic Spinal Cord Injury: A Clinical Pilot Study for Safety and Feasibility. Neurosurgery. 2016; 79(2):E305-12. DOI: 10.1227/NEU.0000000000001283. View

18.

Zhou H, Su J, Hu X, Zhou C, Li H, Chen Z . Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice. Cell. 2020; 181(3):590-603.e16. DOI: 10.1016/j.cell.2020.03.024. View

19.

Su Z, Niu W, Liu M, Zou Y, Zhang C . In vivo conversion of astrocytes to neurons in the injured adult spinal cord. Nat Commun. 2014; 5:3338. PMC: 3966078. DOI: 10.1038/ncomms4338. View

20.

Zong L, Zhu Y, Liang R, Zhao H . Gap junction mediated miRNA intercellular transfer and gene regulation: A novel mechanism for intercellular genetic communication. Sci Rep. 2016; 6:19884. PMC: 4728487. DOI: 10.1038/srep19884. View