PMID- 33864569
OWN - NLM
STAT- MEDLINE
DCOM- 20210906
LR  - 20210906
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 476
IP  - 8
DP  - 2021 Aug
TI  - 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.
PG  - 3191-3205
LID - 10.1007/s11010-021-04155-9 [doi]
AB  - 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-beta1, ACAN, BMP2, and GDF5. 
      Immunocytochemical staining showed positive expression of chondrogenic proteins 
      SOX9, TGF-beta1, TGF-beta2, 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-beta1, and TGF-beta2. 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.
FAU - Ekram, Sobia
AU  - Ekram S
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi, 
      75270, Pakistan.
FAU - Khalid, Shumaila
AU  - Khalid S
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi, 
      75270, Pakistan.
FAU - Bashir, Imtiaz
AU  - Bashir I
AD  - Zainab Panjwani Memorial Hospital, Mohammadali Habib Road, Numaish Karachi, 
      74800, Pakistan.
FAU - Salim, Asmat
AU  - Salim A
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi, 
      75270, Pakistan.
FAU - Khan, Irfan
AU  - Khan I
AUID- ORCID: 0000-0003-1878-7836
AD  - Dr. Panjwani Center for Molecular Medicine and Drug Research, International 
      Center for Chemical and Biological Sciences, University of Karachi, Karachi, 
      75270, Pakistan. khan@iccs.edu.
LA  - eng
GR  - 7083/Higher Education Commision, Pakistan/
PT  - Journal Article
DEP - 20210417
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - *Chondrogenesis
MH  - Humans
MH  - Inflammation/etiology/metabolism/pathology/*prevention & control
MH  - Intervertebral Disc/*cytology
MH  - Intervertebral Disc Degeneration/metabolism/pathology/*therapy
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/methods
MH  - Mesenchymal Stem Cells/*cytology
MH  - Pain/etiology/metabolism/pathology/*prevention & control
MH  - Rats
MH  - Rats, Wistar
MH  - *Regeneration
MH  - Signal Transduction
MH  - Umbilical Cord/cytology
OTO - NOTNLM
OT  - Chondroprogenitor cells
OT  - Gene expression
OT  - Inflammation
OT  - Intervertebral disc
OT  - Mesenchymal stem cells
OT  - Pain
OT  - Regeneration
EDAT- 2021/04/18 06:00
MHDA- 2021/09/07 06:00
CRDT- 2021/04/17 12:09
PHST- 2020/10/18 00:00 [received]
PHST- 2021/04/02 00:00 [accepted]
PHST- 2021/04/18 06:00 [pubmed]
PHST- 2021/09/07 06:00 [medline]
PHST- 2021/04/17 12:09 [entrez]
AID - 10.1007/s11010-021-04155-9 [pii]
AID - 10.1007/s11010-021-04155-9 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2021 Aug;476(8):3191-3205. doi: 10.1007/s11010-021-04155-9. 
      Epub 2021 Apr 17.