PMID- 34285277
OWN - NLM
STAT- MEDLINE
DCOM- 20211110
LR  - 20230204
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Jul 20
TI  - A comparative study of mesenchymal stem cell transplantation and NTG-101 
      molecular therapy to treat degenerative disc disease.
PG  - 14804
LID - 10.1038/s41598-021-94173-w [doi]
LID - 14804
AB  - Cellular replacement therapy using mesenchymal stem cells (MSCs) and/or the 
      delivery of growth factors are at the forefront of minimally invasive biological 
      treatment options for Degenerative Disc Disease (DDD). In this study, we compared 
      the therapeutic potential of a novel drug candidate, NTG-101 to MSCs, including 
      rat cartilage derived stem cells (rCDSCs), bone marrow stem cells (rBMSCs) and 
      human Umbilical Cord Derived Mesenchymal Stem Cells (hUCMSCs) for the treatment 
      of DDD. We induced DDD using a validated image-guided needle puncture injury in 
      rat-tail IVDs. Ten weeks post-injury, animals were randomized and injected with 
      MSCs, NTG-101 or vehicle. At the end of the study, histological analysis of the 
      IVD-Nucleus Pulposus (NPs) injected with NTG-101 or rCDSCs showed a healthy or 
      mild degenerative phenotype in comparison to vehicle controls. 
      Immunohistochemical analysis revealed strong expression of aggrecan, collagen 2, 
      brachyury and Oct4 in IVD-NPs injected with NTG-101. Our results also 
      demonstrated suppression of inflammation induced p38 and NFkappaB resulting in 
      inhibition of catabolic genes, but activation of Smad-2/3, Erk-1/2 and 
      Akt-dependent signaling inducing anabolic genes in IVD-NP on treatment with 
      NTG-101. In conclusion, a single injection of NTG-101 into the degenerative disc 
      demonstrated superior benefits compared to stem cell transplantation.
CI  - (c) 2021. The Author(s).
FAU - Matta, Ajay
AU  - Matta A
AD  - Notogen Inc., Toronto, Ontario, Canada.
FAU - Karim, Muhammad Zia
AU  - Karim MZ
AD  - Notogen Inc., Toronto, Ontario, Canada.
FAU - Gerami, Hoda
AU  - Gerami H
AD  - Notogen Inc., Toronto, Ontario, Canada.
FAU - Benigno, Bettina
AU  - Benigno B
AD  - Notogen Inc., Toronto, Ontario, Canada.
FAU - Erwin, W Mark
AU  - Erwin WM
AD  - Notogen Inc., Toronto, Ontario, Canada. mark.erwin@utoronto.ca.
AD  - Department of Surgery, University of Toronto, Toronto, Ontario, Canada. 
      mark.erwin@utoronto.ca.
AD  - Canadian Memorial Chiropractic College, Toronto, Ontario, Canada. 
      mark.erwin@utoronto.ca.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210720
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (CCN2 protein, human)
RN  - 0 (Recombinant Proteins)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*cytology
MH  - Cartilage/*cytology
MH  - Cells, Cultured
MH  - Connective Tissue Growth Factor/genetics/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Intervertebral Disc Degeneration/*therapy
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mesenchymal Stem Cells/cytology
MH  - Random Allocation
MH  - Rats
MH  - Recombinant Proteins/*administration & dosage/pharmacology
MH  - Transforming Growth Factor beta1/genetics/metabolism
MH  - Umbilical Cord/*cytology
PMC - PMC8292352
COIS- AM, MK, HG, BB, WME Stock ownership Notogen, Inc. AM, MK, HG, BB and WME Salary 
      support Notogen, Inc., WME partial salary support via Canadian Memorial 
      Chiropractic College.
EDAT- 2021/07/22 06:00
MHDA- 2021/11/11 06:00
PMCR- 2021/07/20
CRDT- 2021/07/21 06:09
PHST- 2020/12/16 00:00 [received]
PHST- 2021/07/07 00:00 [accepted]
PHST- 2021/07/21 06:09 [entrez]
PHST- 2021/07/22 06:00 [pubmed]
PHST- 2021/11/11 06:00 [medline]
PHST- 2021/07/20 00:00 [pmc-release]
AID - 10.1038/s41598-021-94173-w [pii]
AID - 94173 [pii]
AID - 10.1038/s41598-021-94173-w [doi]
PST - epublish
SO  - Sci Rep. 2021 Jul 20;11(1):14804. doi: 10.1038/s41598-021-94173-w.