Modulating experimental diabetes by treatment with cytosolic extract from the regenerating pancreas

Hardikar, Anandwardhan A.; Bhonde, Ramesh

doi:10.1016/s0168-8227(99)00098-4

Cited by 25 publications

(17 citation statements)

References 19 publications

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“…It can also be noted that heat-inactivated PCCS did not cause reversal or regeneration either. It was shown earlier in our lab that CE from regenerating pancreas induces normoglycemia and a reversal of experimental diabetes in mice, and our current findings concur with this [29]. The ability of CE derived from the cell pellet to induce transient normoglycemia indicates further that the nesidioblastotic factor is produced by the pancreatic cells, while the supernatant from the same culture induces a stable reversal of diabetes (Table 1).…”

Section: Discussionsupporting

confidence: 91%

“…It has also been shown that tissue extract from cellophane-wrapped pancreas contains protein(s) exhibiting trophic effects on pancreatic tissue including islet cell regeneration [25][26][27][28]. Based on these lines, Hardikar et al from this lab reported in 1999 a reversal of diabetes following serial injections of cytosolic extract from regenerating pancreas [29].…”

Section: Introductionmentioning

confidence: 99%

“…Studies carried out by us and other groups have prompted us to hypothesize that the factor(s) leading to the regeneration of pancreas and restoration of islet mass are either secreted by or are present within the pancreatic milieu itself [11,20,29]. For verification of this hypothesis, we studied the effects of serial intraperitoneal injections of PCCS and pancreatic cell cytosolic extract (CE) from normal pancreas, along with appropriate controls, on the hyperglycemic status of STZ-diabetic mice in vivo and the potential of PCCS to trigger neo islet formation from intra-islet precursor cell monolayer in vitro, and our findings confirm this hypothesis.…”

Section: Introductionmentioning

confidence: 99%

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Existence of Islet Regenerating Factors within the Pancreas

Kanitkar¹,

Bhonde²

2004

Rev Diab Stud

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■ AbstractReduction in the functional mass of β-cells is a common denominator in most forms of diabetes. Since the replicative potential of β-cells is limited, the search for factors that trigger islet neogenesis becomes imperative. Here we tested the hypothesis that regenerating factors for the pancreas are either secreted by or present within the pancreatic milieu itself. For this purpose, we intraperitoneally injected pancreatic cell culture supernatant (PCCS), from normal pancreas, into streptozotocin(STZ)-induced diabetic mice for 15 consecutive days. The PCCS-treated mice showed sustained reversal in 77.77% of experimental diabetic mice as evidenced by restoration of normoglycemia, increase in serum insulin levels and occurrence of neo islets in histopathological studies during a two month follow up, as opposed to the control diabetic mice which remained hyperglycemic throughout. In order to examine the potential of PCCS to bring about the regeneration of islets, we treated intra-islet precursor cells with PCCS in vitro, which led to the neogenesis of islets as evidenced by dithiozone and insulin immunostaining. These findings substantiate our hypothesis and make the search for regenerative factors converge towards the pancreas and its immediate surroundings. Such regenerative approaches, in combination with other therapeutic strategies to promote islet neogenesis may, in future, provide a cure and/or better means for the control and management of diabetes.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Existence of Islet Regenerating Factors within the Pancreas

Kanitkar¹,

Bhonde²

2004

Rev Diab Stud

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“…Among these factors, some endogenous proteins were identified by high-throughput transcriptome and proteome screens of regenerating pancreata [87][88][89][90]. Whole pancreatic extracts after injury appear to promote b-cell mass augmentation in mice treated with STZ [91,92]. Specifically, two proteins of the Reg family, Reg3 (formerly named INGAP) and PSP/Reg, isolated from pancreatic extracts after cellophane wrapping or 90% partial PX, respectively, were shown to stimulate b-cell growth [93][94][95][96].…”

Section: Box 2 Biomolecules For B-cell Regenerationmentioning

confidence: 99%

β-Cell regeneration: the pancreatic intrinsic faculty

Desgraz¹,

Bonal²,

Herrera³

2011

Trends in Endocrinology & Metabolism

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“…Pancreatectomy has already been established as a model of experimental diabetes [24], and substantial regeneration of both exocrine and endocrine pancreas after 90% pancreatectomy has been documented [25]. It is believed that paracrine or cytosolic factors released from the regenerating pancreas are responsible for inducing islet neogenesis that ultimately resulted in the regeneration of the pancreas [26,27]. Rat pancreatic extract (RPE) from a regenerating pancreas is also known to simulate the microenvironment in vitro, inducing MSCs to differentiate into insulinproducing cells [28,29].…”

Section: Abbreviationsmentioning

confidence: 99%

Mesenchymal Stem Cells Derived from Bone Marrow of Diabetic Patients Portrait Unique Markers Influenced by the Diabetic Microenvironment

Phadnis¹,

Ghaskadbi²,

Hardikar³

et al. 2009

Rev Diabet Stud

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■ AbstractCellular microenvironment is known to play a critical role in the maintenance of human bone marrow-derived mesenchymal stem cells (BM-MSCs). It was uncertain whether BM-MSCs obtained from a 'diabetic milieu' (dBM-MSCs) offer the same regenerative potential as those obtained from healthy (non-diabetic) individuals (hBM-MSCs). To investigate the effect of diabetic microenvironment on human BMMSCs, we isolated and characterized these cells from diabetic patients (dBM-MSCs). We found that dBM-MSCs expressed mesenchymal markers such as vimentin, smooth muscle actin, nestin, fibronectin, CD29, CD44, CD73, CD90, and CD105. These cells also exhibited multilineage differentiation potential, as evident from the generation of adipocytes, osteocytes, and chondrocytes when exposed to lineage specific differentiation media. Although the cells were similar to hBM-MSCs, 6% (3/54) of dBM-MSCs expressed proinsulin/C-peptide. Emanating from the diabetic microenvironmental milieu, we analyzed whether in vitro reprogramming could afford the maturation of the islet-like clusters (ICAs) derived from dBM-MSCs. Upon mimicking the diabetic hyperglycemic niche and the supplementation of fetal pancreatic extract, to differentiate dBM-MSCs into pancreatic lineage in vitro, we observed rapid differentiation and maturation of dBM-MSCs into islet-like cell aggregates. Thus, our study demonstrated that diabetic hyperglycemic microenvironmental milieu plays a major role in inducing the differentiation of human BM-MSCs in vivo and in vitro.

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Modulating experimental diabetes by treatment with cytosolic extract from the regenerating pancreas

Cited by 25 publications

References 19 publications

Existence of Islet Regenerating Factors within the Pancreas

Existence of Islet Regenerating Factors within the Pancreas

β-Cell regeneration: the pancreatic intrinsic faculty

Mesenchymal Stem Cells Derived from Bone Marrow of Diabetic Patients Portrait Unique Markers Influenced by the Diabetic Microenvironment

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