2. Academic Validation
  3. The Efficiency of Neurospheres Derived from Human Wharton's Jelly Mesenchymal Stem Cells for Spinal Cord Injury Regeneration in Rats

The Efficiency of Neurospheres Derived from Human Wharton's Jelly Mesenchymal Stem Cells for Spinal Cord Injury Regeneration in Rats

  • Int J Mol Sci. 2023 Feb 14;24(4):3846. doi: 10.3390/ijms24043846.
Sirilak Somredngan 1,  Kasem Theerakittayakorn 1,  Hong Thi Nguyen 1 2,  Apichart Ngernsoungnern 3,  Piyada Ngernsoungnern 3,  Pishyaporn Sritangos 3,  Mariena Ketudat-Cairns 4,  Sumeth Imsoonthornruksa 4,  Nattawut Keeratibharat 5,  Rangsirat Wongsan 6,  Ruttachuk Rungsiwiwut 7,  Rangsun Parnpai 1
Affiliations

Affiliations

  • 1 Embryo Technology and Stem Cell Research Center, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
  • 2 Laboratory of Embryo Technology, Institute of Biotechnology, Vietnam Academy of Science and Technology, Hanoi 100000, Vietnam.
  • 3 School of Preclinical Sciences, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
  • 4 School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
  • 5 School of Surgery, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
  • 6 The Center for Scientific and Technological Equipment, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
  • 7 Department of Anatomy, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
PMID: 36835256 DOI: 10.3390/ijms24043846
Abstract

Spinal cord injury (SCI) causes inflammation and neuronal degeneration, resulting in functional movement loss. Since the availability of SCI treatments is still limited, stem cell therapy is an alternative clinical treatment for SCI and neurodegenerative disorders. Human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) are an excellent option for cell therapy. This study aimed to induce hWJ-MSCs into neural stem/progenitor cells in sphere formation (neurospheres) by using neurogenesis-enhancing small molecules (P7C3 and Isx9) and transplant to recover an SCI in a rat model. Inducted neurospheres were characterized by immunocytochemistry (ICC) and gene expression analysis. The best condition group was selected for transplantation. The results showed that the neurospheres induced by 10 µM Isx9 for 7 days produced neural stem/progenitor cell markers such as Nestin and β-tubulin 3 through the Wnt3A signaling pathway regulation markers (β-catenin and NeuroD1 gene expression). The neurospheres from the 7-day Isx9 group were selected to be transplanted into 9-day-old SCI rats. Eight weeks after transplantation, rats transplanted with the neurospheres could move normally, as shown by behavioral tests. MSCs and neurosphere cells were detected in the injured spinal cord tissue and produced neurotransmitter activity. Neurosphere-transplanted rats showed the lowest cavity size of the SCI tissue resulting from the injury recovery mechanism. In conclusion, hWJ-MSCs could differentiate into neurospheres using 10 µM Isx9 media through the Wnt3A signaling pathway. The locomotion and tissue recovery of the SCI rats with neurosphere transplantation were better than those without transplantation.

Keywords

human umbilical cord Wharton’s jelly-derived mesenchymal stem cells; neurospheres; recovery; spinal cord injury; transplantation.

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