Stem Cells in Clinical Trials on Neurological Disorders: Trends in Stem Cells Origins, Indications, and Status of the Clinical Trials

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Oct 14

PMID 36232760

Authors

Eugenia D Namiot

Jenni Viivi Linnea Niemi

Vladimir N Chubarev

Vadim V Tarasov

Helgi B Schioth

Affiliations

Soon will be listed here.

Abstract

Neurological diseases can significantly reduce the quality and duration of life. Stem cells provide a promising solution, not only due to their regenerative features but also for a variety of other functions, including reducing inflammation and promoting angiogenesis. Although only hematopoietic cells have been approved by the FDA so far, the number of trials continues to expand. We analyzed 492 clinical trials and illustrate the trends in stem cells origins, indications, and phase and status of the clinical trials. The most common neurological disorders treated with stem cells were injuries of brain, spinal cord, and peripheral nerves (14%), stroke (13%), multiple sclerosis (12%), and brain tumors (11%). Mesenchymal stem cells dominated (83%) although the choice of stem cells was highly dependent on the neurological disorder. Of the 492 trials, only two trials have reached phase 4, with most of all other trials being in phases 1 or 2, or transitioning between them (83%). Based on a comparison of the obtained results with similar works and further analysis of the literature, we discuss some of the challenges and future directions of stem cell therapies in the treatment of neurological diseases.

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References

Berebichez-Fridman R, Montero-Olvera P . Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review. Sultan Qaboos Univ Med J. 2019; 18(3):e264-e277. PMC: 6307657. DOI: 10.18295/squmj.2018.18.03.002. View

Andrews J, Jackson C, Heiman-Patterson T, Bettica P, Brooks B, Pioro E . Real-world evidence of riluzole effectiveness in treating amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2020; 21(7-8):509-518. DOI: 10.1080/21678421.2020.1771734. View

Mukai T, Tojo A, Nagamura-Inoue T . Mesenchymal stromal cells as a potential therapeutic for neurological disorders. Regen Ther. 2018; 9:32-37. PMC: 6222283. DOI: 10.1016/j.reth.2018.08.001. View

Miao X, Wu X, Shi W . Umbilical cord mesenchymal stem cells in neurological disorders: A clinical study. Indian J Biochem Biophys. 2015; 52(2):140-6. View

Yuan S, Martin J, Elia J, Flippin J, Paramban R, Hefferan M . Cell-surface marker signatures for the isolation of neural stem cells, glia and neurons derived from human pluripotent stem cells. PLoS One. 2011; 6(3):e17540. PMC: 3047583. DOI: 10.1371/journal.pone.0017540. View

Yamazaki K, Kawabori M, Seki T, Houkin K . Clinical Trials of Stem Cell Treatment for Spinal Cord Injury. Int J Mol Sci. 2020; 21(11). PMC: 7313002. DOI: 10.3390/ijms21113994. View

Lv F, Tuan R, Cheung K, Leung V . Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells. 2014; 32(6):1408-19. DOI: 10.1002/stem.1681. View

Kabat M, Bobkov I, Kumar S, Grumet M . Trends in mesenchymal stem cell clinical trials 2004-2018: Is efficacy optimal in a narrow dose range?. Stem Cells Transl Med. 2019; 9(1):17-27. PMC: 6954709. DOI: 10.1002/sctm.19-0202. View

Serrenho I, Rosado M, Dinis A, Cardoso C, Graos M, Manadas B . Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Systematic Review of Preclinical Studies. Int J Mol Sci. 2021; 22(6). PMC: 8003344. DOI: 10.3390/ijms22063142. View

10.

Jiang W, Xu J . Immune modulation by mesenchymal stem cells. Cell Prolif. 2019; 53(1):e12712. PMC: 6985662. DOI: 10.1111/cpr.12712. View

11.

Andia I, Maffulli N, Burgos-Alonso N . Stromal vascular fraction technologies and clinical applications. Expert Opin Biol Ther. 2019; 19(12):1289-1305. DOI: 10.1080/14712598.2019.1671970. View

12.

Park Y, Niizuma K, Mokin M, Dezawa M, Borlongan C . Cell-Based Therapy for Stroke: Musing With Muse Cells. Stroke. 2020; 51(9):2854-2862. DOI: 10.1161/STROKEAHA.120.030618. View

13.

Song N, Scholtemeijer M, Shah K . Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential. Trends Pharmacol Sci. 2020; 41(9):653-664. PMC: 7751844. DOI: 10.1016/j.tips.2020.06.009. View

14.

Andrzejewska A, Dabrowska S, Lukomska B, Janowski M . Mesenchymal Stem Cells for Neurological Disorders. Adv Sci (Weinh). 2021; 8(7):2002944. PMC: 8024997. DOI: 10.1002/advs.202002944. View

15.

Pluchino S, Smith J, Peruzzotti-Jametti L . Promises and Limitations of Neural Stem Cell Therapies for Progressive Multiple Sclerosis. Trends Mol Med. 2020; 26(10):898-912. DOI: 10.1016/j.molmed.2020.04.005. View

16.

Fleifel D, Rahmoon M, AlOkda A, Nasr M, Elserafy M, El-Khamisy S . Recent advances in stem cells therapy: A focus on cancer, Parkinson's and Alzheimer's. J Genet Eng Biotechnol. 2019; 16(2):427-432. PMC: 6354001. DOI: 10.1016/j.jgeb.2018.09.002. View

17.

Ikegame Y, Yamashita K, Hayashi S, Mizuno H, Tawada M, You F . Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy. Cytotherapy. 2011; 13(6):675-85. DOI: 10.3109/14653249.2010.549122. View

18.

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

19.

Wang Y, Tang Z, Gu P . Stem/progenitor cell-based transplantation for retinal degeneration: a review of clinical trials. Cell Death Dis. 2020; 11(9):793. PMC: 7511341. DOI: 10.1038/s41419-020-02955-3. View

20.

Sun C, Serra C, Lee G, Wagner K . Stem cell-based therapies for Duchenne muscular dystrophy. Exp Neurol. 2019; 323:113086. PMC: 6899334. DOI: 10.1016/j.expneurol.2019.113086. View