Local Growth Factors Are Beneficial for the Autonomic Reinnervation of Transplanted Islets in Rats

Reimer, Martina Kvist; Mokshagundam, Sri Prakash L.; Wyler, Karen; Sundler, F.; Åhrén, Bo; Stagner, John I.

doi:10.1097/00006676-200305000-00014

Cited by 36 publications

(23 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, studies in pigs have shown that the vascularization and reinnervation of skin grafts are coordinated (5). It is likely that growth factors are involved in the coordinated reinnervation and vascularization of transplants (30,31) and may contribute to innervation of the ectopic endometrial growths. Thus, of relevance to ENDO in women, Anaf et al (7) found that nerve growth factor expression was greater in deeply infiltrating adenomyotic endometrial nodules when compared with other ectopic endometrial growths and that these nodules were located closer to nerve fibers.…”

Section: Discussionmentioning

confidence: 99%

“…Studies of transplanted tissues indicate that their reinnervation, particularly by sympathetic fibers, can be important not only for better functioning of transplanted tissues but also their survival (5,31,39,40). Furthermore, the fact that the sensory fibers expressing SP and CGRP are anatomically intimate with the vasculature of the cyst wall and extend terminals among the epithelial cells lining the cyst lumen suggests they have both sensory and efferent functions.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Innervation of ectopic endometrium in a rat model of endometriosis

Berkley

Dmitrieva

Curtis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

195

161

View full text Add to dashboard Cite

Endometriosis (ENDO) is a disorder in which vascularized growths of endometrial tissue occur outside the uterus. Its symptoms include reduced fertility and severe pelvic pain. Mechanisms that maintain the ectopic growths and evoke symptoms are poorly understood. One factor not yet considered is that the ectopic growths develop their own innervation. Here, we tested the hypothesis that the growths develop both an autonomic and a sensory innervation. We used a rat model of surgically induced ENDO whose growths mimic those in women. Furthermore, similar to women with ENDO, such rats exhibit reduced fertility and increased pelvic nociception. The ENDO was induced by autotransplanting, on mesenteric cascade arteries, small pieces of uterus that formed vascularized cysts. The cysts and healthy uterus were harvested from proestrous rats and immunostained using the pan-neuronal marker PGP9.5 and specific markers for calcitonin gene-related peptide (CGRP) (sensory C and A␦ fibers), substance P (SP) (sensory C and A␦ fibers) and vesicular monoamine transporter (sympathetic fibers). Cysts (like the uterus) were robustly innervated, with many PGP9.5-stained neurites accompanying blood vessels and extending into nearby luminal epithelial layers. CGRP-, SP-, and vesicular monoamine transporter-immunostained neurites also were observed, with CGRP and SP neurites extending the furthest into the cyst lining. These results demonstrate that ectopic endometrial growths develop an autonomic and sensory innervation. This innervation could contribute not only to symptoms associated with ENDO but also to maintenance of the ectopic growths.uterus ͉ fertility ͉ pain ͉ transplant ͉ neuropeptides

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Innervation of ectopic endometrium in a rat model of endometriosis

Berkley

Dmitrieva

Curtis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

195

161

View full text Add to dashboard Cite

show abstract

“…When islets and NCSCs were co-cultured in the upper compartment, no beta cells proliferated in the lower compartment that contained islets only (n03-4, p>0.1 for all comparisons). White bars indicate an empty insert, hatched bars an insert containing NCSCs and black bars, an insert containing a coculture of islets and NCSCs mice [4,38]. Interestingly, not only beta cells but also nerve structures seem to be affected by the autoimmune assault seen during type 1 diabetes, and nerves disappear before any loss of beta cells occurs in type 1 diabetic BB rats [5,6], which may hamper beta cell regenerative capacity.…”

Section: Discussionmentioning

confidence: 99%

Differentiating neural crest stem cells induce proliferation of cultured rodent islet beta cells

et al. 2012

View full text Add to dashboard Cite

Aims/hypothesis Efficient stimulation of cycling activity in cultured beta cells would allow the design of new strategies for cell therapy in diabetes. Neural crest stem cells (NCSCs) play a role in beta cell development and maturation and increase the beta cell number in co-transplants. The mechanism behind NCSC-induced beta cell proliferation and the functional capacity of the new beta cells is not known. Methods We developed a new in vitro co-culture system that enables the dissection of the elements that control the cellular interactions that lead to NCSC-dependent increase in islet beta cells.Results Mouse NCSCs were cultured in vitro, first in medium that stimulated their proliferation, then under conditions that supported their differentiation. When mouse islet cells were cultured together with the NCSCs, more than 35% of the beta cells showed cycle activity. This labelling index is more than tenfold higher than control islets cultured without NCSCs. Beta cells that proliferated under these culture conditions were fully glucose responsive in terms of insulin secretion. NCSCs also induced beta cell proliferation in islets isolated from 1-year-old mice, but not in dissociated islet cells isolated from human donor pancreas tissue. To stimulate beta cell proliferation, NCSCs need to be in intimate contact with the beta cells. Conclusions/interpretation Culture of islet cells in contact with NCSCs induces highly efficient beta cell proliferation. The reported culture system is an excellent platform for further dissection of the minimal set of factors needed to drive this process and explore its potential for translation to diabetes therapy.

show abstract

“…Ngfb promotes b-cell survival 33,34 and increases islet morphogenesis. 35 RT-PCR analysis revealed lower Ngfb expression in BBdp rats (Figure 6d), which could further contribute to the reduced capacity for b-cell survival and islet expansion.…”

Section: Decreased Ngfb and Pdx1 Gene Expressionmentioning

confidence: 99%

Increased islet neogenesis without increased islet mass precedes autoimmune attack in diabetes-prone rats

Kauri¹,

Wang²,

Patrick

et al. 2007

Laboratory Investigation

View full text Add to dashboard Cite

We reported previously that young BioBreeding diabetes-prone (BBdp) rats display increased neogenic extra-islet insulin þ clusters (EICs, o4 insulin þ cells) without an increase in b-cell mass. Therefore, we investigated the possibility that abnormal islet expansion occurs in BBdp rats before the appearance of islet inflammation. Islet expansion was analyzed in pancreata from 14 to 45 day BBdp and control (BioBreeding control, BBc) rats using immunohistochemistry, morphometry, laser capture microdissection and reverse transcriptase-PCR. mRNA expression for Neurogenin-3, a developmental marker of endocrine progenitors, was three-fold greater in EIC of weanling BBdp and BBc rats compared with islet cells. With increasing age (14-30 days), Neurogenin-3 expression decreased in EIC and increased in islets. In BBdp rats, EIC number and b-cell proliferation within EIC was greater compared with BBc animals; apoptosis did not differ. The area of small and medium islets in BBdp rats was greater than BBc rats between 14 and 30 days, but this did not result in increased total islet area or b-cell mass. In addition, the number and area of very large islets was low at 45 days. The frequency of proliferating b-cells decreased with increasing islet size in BBdp but was constant in BBc rats. Cell cycle analysis of islets revealed more G1 cells and fewer G2 cells in BBdp rats. The ratio of cyclinD2/Cdkn1a, genes that respectively promote or inhibit cell cycle progression, was decreased in BBdp islets. These results suggest that despite increased islet neogenesis, the capacity for islet expansion in diabetes-prone rats is compromised possibly due to decreased proliferative capacity with increasing islet size associated with a partial block at the G1/S cell cycle boundary in islet cells.

show abstract

Local Growth Factors Are Beneficial for the Autonomic Reinnervation of Transplanted Islets in Rats

Abstract: Local growth factor treatment has a beneficial effect on autonomic reinnervation as well as islet integrity and survival of the graft after islet transplantation in rats.

Cited by 36 publications

References 29 publications

Innervation of ectopic endometrium in a rat model of endometriosis

Innervation of ectopic endometrium in a rat model of endometriosis

Differentiating neural crest stem cells induce proliferation of cultured rodent islet beta cells

Increased islet neogenesis without increased islet mass precedes autoimmune attack in diabetes-prone rats

Contact Info

Product

Resources

About