Isolation and in vitro characterization of pancreatic progenitor cells from the islets of diabetic monkey models

Zou, Chunlin; Suen, Po Man; Zhang, Ying; Wang, Zeyu; Chan, Piu; Leung, Po Sing; Zhang, Y. Alex

doi:10.1016/j.biocel.2005.12.012

Cited by 11 publications

(13 citation statements)

References 24 publications

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“…We have previously reported that PPCs can be isolated from fresh pancreata of diabetic monkeys and expanded for more than 10 passages in vitro 22 . Here, we examined the expression of pancreatic and stem cell markers in these progenitor cells by immunofluorescence staining.…”

Section: Resultsmentioning

confidence: 99%

“…However, few studies have considered the temporal relationship between the loss of SPION-labeled IPCs on MRI and the decrease in blood insulin or C-peptide levels, and few have demonstrated that SPION-based MR tracking is more sensitive for timely detection of IPC loss than measuring blood insulin or C-peptide levels. In the present study, we differentiated SPION-labeled monkey PPCs to IPCs using a previously described method 22, 28 , and we transplanted cultured autologous IPCs into the liver of STZ-induced diabetic monkeys without immunosuppression. To rule out the possibility that the observed increase in blood C-peptide levels was due to spontaneous β-cell regeneration, insulin immunostaining was performed in pancreas sections.…”

Section: Discussionmentioning

confidence: 99%

“…PPCs were isolated as reported previously 22 and propagated in RPMI 1640 medium (Life Technologies, Carlsbad, CA, USA) supplemented with 10% FBS (Life Technologies), 20 ng/ml bFGF, and 20 ng/ml EGF (both from R&D Systems, Minneapolis, MN, USA).…”

Section: Methodsmentioning

confidence: 99%

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MRI tracking of autologous pancreatic progenitor-derived insulin-producing cells in monkeys

Zou

Lü

Teng

et al. 2017

Sci Rep

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Insulin-producing cells (IPCs) derived from a patient’s own stem cells offer great potential for autologous transplantation in diabetic patients. However, the limited survival of engrafted cells remains a bottleneck in the application of this strategy. The present study aimed to investigate whether nanoparticle-based magnetic resonance (MR) tracking can be used to detect the loss of grafted stem cell-derived IPCs in a sensitive and timely manner in a diabetic monkey model. Pancreatic progenitor cells (PPCs) were isolated from diabetic monkeys and labeled with superparamagnetic iron oxide nanoparticles (SPIONs). The SPION-labeled cells presented as hypointense signals on MR imaging (MRI). The labeling procedure did not affect the viability or IPC differentiation of PPCs. Importantly, the total area of the hypointense signal caused by SPION-labeled IPCs on liver MRI decreased before the decline in C-peptide levels after autotransplantation. Histological analysis revealed no detectable immune response to the grafts and many surviving insulin- and Prussian blue-positive cell clusters on liver sections at one year post-transplantation. Collectively, this study demonstrates that SPIO nanoparticles can be used to label stem cells for noninvasive, sensitive, longitudinal monitoring of stem cell-derived IPCs in large animal models using a conventional MR imager.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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MRI tracking of autologous pancreatic progenitor-derived insulin-producing cells in monkeys

Zou

Lü

Teng

et al. 2017

Sci Rep

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“…Adherent cells were then placed in restrictive medium (0.5% FBS) for 4 weeks acquiring characteristic spindle-shaped fibroblastic morphology (Figure 1 A). In the third phase, FBS was increased to 10% and bFGF and EGF growth factors were added to favour SC expansion (31). The rapidly proliferating cells expanded 3- to 5-fold as the cells grew to confluency over about 2 weeks (Figure 1 B).…”

Section: Resultsmentioning

confidence: 99%

Persistent circulating human insulin in sheep transplanted in utero with human mesenchymal stem cells

Ersek

Pixley

Goodrich

et al. 2010

Experimental Hematology

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Objective-To determine if mesenchymal stem cells (MSC) derived from human fetal pancreatic tissue (pMSC) would engraft and differentiate in sheep pancreas following transplantation in utero.Methods-A three-step culture system was established for generating human fetal pMSC. Sheep fetuses were transplanted during the fetal transplant receptivity period with human pMSC and evaluated for in situ and functional engraftment in their pancreas, liver and bone marrow.Results-Isolation and expansion of adherent cells from the human fetal pancreas yielded a cell population with morphologic and phenotypic characteristics similar to MSC derived from bone marrow. This putative stem cell population could undergo multilineage differentiation in vitro. Three to 27 months after fetal transplantation, the pancreatic engraftment frequency (chimeric index) was 79% while functional engraftment was noted in 50% of transplanted sheep. Hepatic and marrow engraftment and expression was noted as well.Conclusion-We have established a procedure for isolation of human fetal pMSC that display characteristics similar to bone marrow derived MSC. In vivo results suggest the pMSC engraft, differentiate and secrete human insulin from the sheep pancreas.

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“…Streptozotocin‐induced diabetes mellitus was injected at a high dose (100 mg/kg) through femoral vein and cynomolgus monkeys were successfully induced with diabetes based on their hyperglycemic conditions, abnormal intravenous glucose tolerance test (IVGTT), insulin and C‐peptide levels as described in a previous paper [34]. The control and STZ‐induced diabetic (STZ‐DM) monkeys were monitored for fasting glucose using Accu‐Chek Blood Glucose Monitor (Roche, Mannheim, Germany) at least five times before experiments with Accu‐Chek Softclix lancet (Roche, Mannheim, Germany).…”

Section: Methodsmentioning

confidence: 99%

The effect of long‐term streptozotocin‐induced diabetes mellitus (STZ‐DM) on cynomolgus (Macaca Fascicularis) monkeys

Zou²,

Yue³

et al. 2009

J of Medical Primatology

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Isolation and in vitro characterization of pancreatic progenitor cells from the islets of diabetic monkey models

Cited by 11 publications

References 24 publications

MRI tracking of autologous pancreatic progenitor-derived insulin-producing cells in monkeys

MRI tracking of autologous pancreatic progenitor-derived insulin-producing cells in monkeys

Persistent circulating human insulin in sheep transplanted in utero with human mesenchymal stem cells

The effect of long‐term streptozotocin‐induced diabetes mellitus (STZ‐DM) on cynomolgus (Macaca Fascicularis) monkeys

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