Biodistribution of allogenic umbilical cord-derived mesenchymal stromal cells after fetal repair of myelomeningocele in an ovine model.
Biodistribution
Fetal surgery
Mesenchymal stromal cells
Myelomeningocele
Ovine model
Tracking
Journal
Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581
Informations de publication
Date de publication:
15 07 2022
15 07 2022
Historique:
received:
26
01
2022
accepted:
25
06
2022
entrez:
15
7
2022
pubmed:
16
7
2022
medline:
20
7
2022
Statut:
epublish
Résumé
Myelomeningocele (MMC) is a spinal cord congenital defect that leads to paraplegia, sphincter disorders and potential neurocognitive disabilities. Prenatal surgery of MMC provides a significant benefit compared to surgery at birth. Mesenchymal stromal cell (MSC) therapy as an adjuvant treatment for prenatal surgery showed promising results in animal experiments which could be considered for clinical use in human fetuses. Despite numerous reassuring studies on the safety of MSCs administration in humans, no study focused on MSCs biodistribution after a local MSCs graft on the fetal spinal cord. The purpose of our study was to assess the biodistribution of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) at birth in lambs who had a prenatal myelomeningocele repair using a fibrin patch seeded with allogenic UC-MSCs. After isolation, UC-MSCs were tagged using a green fluorescent protein (GFP)-containing lentiviral vector. MMC defects were surgically created at 75 days of gestation and repaired 15 days later using UC-MSCs patch. Lambs were delivered at 142 days and sacrificed. DNA extraction was performed among biopsies of the different organs and q-PCR analysis was used to detect the expression of GFP (GFP DNA coding sequence). In our 6 surviving lambs grafted with UC-MSCs, GFP lentivirus genomic DNA was not detected in the organs. These reassuring data will support translational application in humans, especially since the first human clinical trial using mesenchymal stromal cells for in-utero treatment of MMC started recently in U.S.A.
Sections du résumé
BACKGROUND
Myelomeningocele (MMC) is a spinal cord congenital defect that leads to paraplegia, sphincter disorders and potential neurocognitive disabilities. Prenatal surgery of MMC provides a significant benefit compared to surgery at birth. Mesenchymal stromal cell (MSC) therapy as an adjuvant treatment for prenatal surgery showed promising results in animal experiments which could be considered for clinical use in human fetuses. Despite numerous reassuring studies on the safety of MSCs administration in humans, no study focused on MSCs biodistribution after a local MSCs graft on the fetal spinal cord.
AIM
The purpose of our study was to assess the biodistribution of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) at birth in lambs who had a prenatal myelomeningocele repair using a fibrin patch seeded with allogenic UC-MSCs.
METHODS
After isolation, UC-MSCs were tagged using a green fluorescent protein (GFP)-containing lentiviral vector. MMC defects were surgically created at 75 days of gestation and repaired 15 days later using UC-MSCs patch. Lambs were delivered at 142 days and sacrificed. DNA extraction was performed among biopsies of the different organs and q-PCR analysis was used to detect the expression of GFP (GFP DNA coding sequence).
RESULTS
In our 6 surviving lambs grafted with UC-MSCs, GFP lentivirus genomic DNA was not detected in the organs.
CONCLUSION
These reassuring data will support translational application in humans, especially since the first human clinical trial using mesenchymal stromal cells for in-utero treatment of MMC started recently in U.S.A.
Identifiants
pubmed: 35841029
doi: 10.1186/s13287-022-02991-0
pii: 10.1186/s13287-022-02991-0
pmc: PMC9284777
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
300Informations de copyright
© 2022. The Author(s).
Références
Stem Cell Res Ther. 2021 Feb 26;12(1):152
pubmed: 33637125
Pediatrics. 2020 Feb;145(2):
pubmed: 31980545
J Pediatr Surg. 2017 Oct 12;:
pubmed: 29122293
Cytotherapy. 2013 Jul;15(7):753-9
pubmed: 23602595
Cell Transplant. 2018 Jun;27(6):907-915
pubmed: 29871514
Stem Cells Int. 2013;2013:387324
pubmed: 24228035
Curr Res Transl Med. 2022 Jan;70(1):103314
pubmed: 34731725
Fetal Diagn Ther. 2021;48(5):381-391
pubmed: 33853064
J Pediatr Surg. 2018 Jun;53(6):1134-1136
pubmed: 29580785
J Gynecol Obstet Hum Reprod. 2021 Nov;50(9):102155
pubmed: 33915336
N Engl J Med. 2011 Mar 17;364(11):993-1004
pubmed: 21306277
PLoS One. 2012;7(10):e47559
pubmed: 23133515
Neural Regen Res. 2020 Sep;15(9):1686-1700
pubmed: 32209773
EClinicalMedicine. 2020 Jan 17;19:100249
pubmed: 31989101
J Pediatr Surg. 2019 Feb;54(2):293-296
pubmed: 30518492
J Pediatr Surg. 2020 Sep;55(9):1941-1946
pubmed: 31672407
Stem Cells Transl Med. 2015 Jun;4(6):659-69
pubmed: 25911465
J Pharmacol Exp Ther. 2021 Nov;379(2):125-133
pubmed: 34373354
J Pediatr Surg. 2019 Jan;54(1):75-79
pubmed: 30529115
Am J Obstet Gynecol. 2018 Feb;218(2):256.e1-256.e13
pubmed: 29246577
Curr Res Transl Med. 2020 Nov;68(4):183-189
pubmed: 32624428
J Surg Res. 2021 Nov;267:660-668
pubmed: 34273796