Human umbilical cord-derived mesenchymal stem cells and their chondroprogenitor derivatives reduced pain and inflammation signaling and promote regeneration in a rat intervertebral disc degeneration model.
Sobia EkramShumaila KhalidImtiaz BashirAsmat SalimIrfan KhanPublished in: Molecular and cellular biochemistry (2021)
Intervertebral disc (IVD) degeneration is an asymptomatic pathophysiological condition and a strong causative factor of low back pain. There is no cure available except spinal fusion and pain management. Stem cell-based regenerative medicine is being considered as an alternative approach to treat disc diseases. The current study aimed to differentiate human umbilical cord-mesenchymal stem cells (hUC-MSCs) into chondrocyte-like cells and to elucidate their feasibility and efficacy in the degenerated IVD rat model. Chondrogenic induction medium was used to differentiate hUC-MSCs into chondroprogenitors. Rat tail IVD model was established with three consecutive coccygeal discs. qPCR was performed to quantify the molecular markers of pain and inflammation. Histological staining was performed to evaluate the degree of regeneration. Induced chondroprogenitors showed the expression of chondrogenic genes, SOX9, TGF-β1, ACAN, BMP2, and GDF5. Immunocytochemical staining showed positive expression of chondrogenic proteins SOX9, TGF-β1, TGF-β2, and Collagen 2. In in vivo study, transplanted chondroprogenitors showed better survival, homing, and distribution in IVD as compared to normal MSCs. Expression of pain and inflammatory genes at day 5 of cell transplantation modulated immune response significantly. The transplanted labeled MSCs and induced chondroprogenitors differentiated into functional nucleus pulposus (NP) cells as evident from co-localization of red (DiI) and green fluorescence for SOX9, TGF-β1, and TGF-β2. Alcian blue and H & E staining showed standard histological features, indicating better preservation of the NP structure and cellularity than degenerated discs. hUC-MSCs-derived chondroprogenitors showed better regeneration potential as compared to normal MSCs. The pain and inflammation genes were downregulated in the treated group as compared to the degenerated IVD.
Keyphrases
- mesenchymal stem cells
- umbilical cord
- pain management
- stem cells
- chronic pain
- oxidative stress
- transforming growth factor
- cell therapy
- poor prognosis
- bone marrow
- diabetic rats
- endothelial cells
- neuropathic pain
- immune response
- induced apoptosis
- high glucose
- transcription factor
- genome wide
- spinal cord
- epithelial mesenchymal transition
- wound healing
- gene expression
- computed tomography
- single cell
- induced pluripotent stem cells
- bioinformatics analysis
- cell cycle arrest
- pluripotent stem cells
- cell death
- risk assessment
- genome wide analysis