UNIGE document Scientific Article
previous document  unige:155356  next document
add to browser collection

Multipotent mesenchymal stromal cells derived from porcine exocrine pancreas improve insulin secretion from juvenile porcine islet cell clusters

Szabó, Luca
Giraud, Marie-Noelle
Egger, Bernhard
show hidden authors show all authors [1 - 11]
Published in Xenotransplantation. 2021, vol. 28, no. 3, e12666
Abstract Neonatal and juvenile porcine islet cell clusters (ICC) present an unlimited source for islet xenotransplantation to treat type 1 diabetes patients. We isolated ICC from pancreata of 14 days old juvenile piglets and characterized their maturation by immunofluorescence and insulin secretion assays. Multipotent mesenchymal stromal cells derived from exocrine tissue of same pancreata (pMSC) were characterized for their differentiation potential and ability to sustain ICC insulin secretion in vitro and in vivo. Isolation of ICC resulted in 142 ± 50 × 103 IEQ per pancreas. Immunofluorescence staining revealed increasing presence of insulin-positive beta cells between day 9 and 21 in culture and insulin content per 500IEC of ICC increased progressively over time from 1178.4 ± 450 µg/L to 4479.7 ± 1954.2 µg/L from day 7 to 14, P < .001. Highest glucose-induced insulin secretion by ICC was obtained at day 7 of culture and reached a fold increase of 2.9 ± 0.4 compared to basal. Expansion of adherent cells from the pig exocrine tissue resulted in a homogenous CD90+ , CD34- , and CD45- fibroblast-like cell population and differentiation into adipocytes and chondrocytes demonstrated their multipotency. Insulin release from ICC was increased in the presence of pMSC and dependent on cell-cell contact (glucose-induced fold increase: ICC alone: 1.6 ± 0.2; ICC + pMSC + contact: 3.2 ± 0.5, P = .0057; ICC + pMSC no-contact: 1.9 ± 0.3; theophylline stimulation: alone: 5.4 ± 0.7; pMSC + contact: 8.4 ± 0.9, P = .013; pMSC no-contact: 5.2 ± 0.7). After transplantation of encapsulated ICC using Ca2+ -alginate (alg) microcapsules into streptozotocin-induced diabetic and immunocompetent mice, transient normalization of glycemia was obtained up to day 7 post-transplant, whereas ICC co-encapsulated with pMSC did not improve glycemia and showed increased pericapsular fibrosis. We conclude that pMSC derived from juvenile porcine exocrine pancreas improves insulin secretion of ICC by direct cell-cell contact. For transplantation purposes, the use of pMSC to support beta-cell function will depend on the development of new anti-fibrotic polymers and/or on genetically modified pigs with lower immunogenicity.
Keywords AnimalsHumansInsulin / metabolismInsulin SecretionIslets of Langerhans Transplantation*Islets of Langerhans* / metabolismMesenchymal Stem Cells*MicePancreas / metabolismPancreasExocrine* / metabolismSwineTransplantationHeterologous
PMID: 33538027
Full text
Article (Published version) (2.1 MB) - document accessible for UNIGE members only Limited access to UNIGE
Research group La transplantation d'îlots de Langerhans (623)
Swiss National Science Foundation: N° 310030E-164520
(ISO format)
MONTANARI, Elisa et al. Multipotent mesenchymal stromal cells derived from porcine exocrine pancreas improve insulin secretion from juvenile porcine islet cell clusters. In: Xenotransplantation, 2021, vol. 28, n° 3, p. e12666. doi: 10.1111/xen.12666 https://archive-ouverte.unige.ch/unige:155356

46 hits

0 download


Deposited on : 2021-10-13

Export document
Format :
Citation style :