Published online Feb 26, 2022. doi: 10.4252/wjsc.v14.i2.163
Peer-review started: February 28, 2021
First decision: April 19, 2021
Revised: May 2, 2021
Accepted: January 6, 2022
Article in press: January 6, 2022
Published online: February 26, 2022
Processing time: 362 Days and 2.9 Hours
Genetic manipulation is now considered the safest and promising approach in the field of regenerative medicine. Mesenchymal stem cells (MSCs) are the potential candidates for the clinical use of genetically engineered stem cells. They are non-immunogenic, proliferative, and possess multiple lineage differentiation potential. Gene modification of MSCs using chondrogenic transcription factors may lead to the use of this strategy to treat debilitating diseases related to cartilage.
Genetic modification of MSCs offers a competent source for the sustained translation of therapeutic proteins. Transfection of human umbilical cord derived MSCs (hUC-MSCs) using chondro-specific transcription factors may lead to enhance chondrogenesis and efficient regeneration of cartilage-related injuries.
The main objective of the study was to analyze the effect of transcription factors Sox-9 and Six-1 in chondrogenesis by transfecting them into hUC-MSCs and determining successful intervertebral disc (IVD) regeneration.
MSCs were isolated from cord tissue and characterized using their specific markers. MSCs were transfected using transcription factors Sox-9 and Six-1. Cell differentiation was analyzed at the transcriptional and translational levels, while the regeneration potential of transfected MSCs was observed by transplanting them into the degenerated rat IVD model. Post-transplantation histology and cell tracking analysis were performed to evaluate cartilage regeneration.
In vitro analysis showed that transcription and translation of chondrogenic markers were significantly higher in transfected MSCs at 24 h, and 21 d in comparison to control MSCs. Transfected MSCs at the site of degenerated IVD differentiated into chondrocytes which secreted chondro-proteins. The cells homed and regenerated the injured cartilage as that of normal cartilage, as evident from immunohistological and histological analyses.
Genetic modification of hUC-MSCs with two chondrogenic transcriptional factors Sox-9 and Six-1 enhances their chondrogenic differentiation. Their synergistic effect on MSCs accelerated the regeneration of degenerated cartilage with complete restoration of tissue architecture.
The present manuscript offers a promising therapeutic approach to revolutionize the treatment of cartilaginous defects and spinal cord injuries. The outcomes discussed in this study accentuates the advances towards the clinical translation of such approaches.