Mechanism of insulin production in canine bone marrow derived mesenchymal stem cells

Takemitsu, Hiroshi; Zhao, Dongwei; Ishikawa, Shingo; Michishita, Masaki; Arai, Toshiro; Yamamoto, Ichiro

doi:10.1016/j.ygcen.2013.04.009

Cited by 9 publications

(10 citation statements)

References 26 publications

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“…Our FACS data are consistent with other studies [ 16 , 27 , 35 ], although immunophenotyping the canine cells involves difficulty because of the limited availability of antibodies which cross-react with the dog [ 12 ]. The expression profile corresponding with those is widely described in the literature for MSCs [ 11 , 12 , 36 ], as shown by our results: positive expression of CD29, CD90 and STRO-1, and lack of expression of hematopoietic markers CD34, CD45, or MHC-II.…”

Section: Discussionsupporting

confidence: 91%

Use of Adipose-Derived Mesenchymal Stem Cells in Keratoconjunctivitis Sicca in a Canine Model

Villatoro

Fernández

Claros

et al. 2015

BioMed Research International

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Keratoconjunctivitis sicca (KCS) or dry eye disease (DED) is an immune-mediated multifactorial disease, with high level of prevalence in humans and dogs. Our aim in this study was to investigate the therapeutic effects of allogeneic adipose-derived mesenchymal stromal cells (Ad-MSCs) implanted around the lacrimal glands in 12 dogs (24 eyes) with KCS, which is refractory to current available treatments. Schirmer tear test (STT) and ocular surface integrity were assessed at 0 (before treatment), 3, 6, and 9 months after treatment. Average STT values and all clinical signs showed a statistically significant change (P < 0.001) during the follow-up with reduction in all ocular parameters scored: ocular discharge, conjunctival hyperaemia, and corneal changes, and there were no signs of regression or worsening. Implanted cells were well tolerated and were effective reducing clinical signs of KCS with a sustained effect during the study period. None of the animals showed systemic or local complications during the study. To our knowledge, this is the first time in literature that implantation of allogeneic Ad-MSCs around lacrimal glands has been found as an effective therapeutic alternative to treat dogs with KCS. These results could reinforce a good effective solution to be extrapolated to future studies in human.

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Section: Discussionsupporting

confidence: 91%

Use of Adipose-Derived Mesenchymal Stem Cells in Keratoconjunctivitis Sicca in a Canine Model

Villatoro

Fernández

Claros

et al. 2015

BioMed Research International

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“…One is to introduce key transcription regulatory factors, such as pancreatic and duodenal homeobox 1 (PDX-1) and β-cell transactivator 2 (Beta2), by genetic engineering to modulate gene expression. The other is to supply specific soluble inducers or small molecule compounds in cell culture medium to initiate and promote β-cell differentiation [ 15 – 17 ]. The efficiency and extent of stem cell differentiation are modulated by the internal genetic program and the external microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Insulin-Producing Cells Differentiated from Human Bone Marrow Mesenchymal Stem Cells In Vitro Ameliorate Streptozotocin-Induced Diabetic Hyperglycemia

et al. 2016

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BackgroundThe two major obstacles in the successful transplantation of islets for diabetes treatment are inadequate supply of insulin-producing tissue and immune rejection. Induction of the differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) into insulin-producing cells (IPCs) for autologous transplantation may alleviate those limitations.MethodshMSCs were isolated and induced to differentiate into IPCs through a three-stage differentiation protocol in a defined media with high glucose, nicotinamide, and exendin-4. The physiological characteristics and functions of IPCs were then evaluated. Next, about 3 × 106 differentiated cells were transplanted into the renal sub-capsular space of streptozotocin (STZ)-induced diabetic nude mice. Graft survival and function were assessed by immunohistochemistry, TUNEL staining and measurements of blood glucose levels in the mice.ResultsThe differentiated IPCs were characterized by Dithizone (DTZ) positive staining, expression of pancreatic β-cell markers, and human insulin secretion in response to glucose stimulation. Moreover, 43% of the IPCs showed L-type Ca2+ channel activity and similar changes in intracellular Ca2+ in response to glucose stimulation as that seen in pancreatic β-cells in the process of glucose-stimulated insulin secretion. Transplantation of functional IPCs into the renal subcapsular space of STZ-induced diabetic nude mice ameliorated the hyperglycemia. Immunofluorescence staining revealed that transplanted IPCs sustainably expressed insulin, c-peptide, and PDX-1 without apparent apoptosis in vivo.ConclusionsIPCs derived from hMSCs in vitro can ameliorate STZ-induced diabetic hyperglycemia, which indicates that these hMSCs may be a promising approach to overcome the limitations of islet transplantation.

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“…Sun and associates could differentiate hBM-MSCs from diabetic patients to form IPCs [41]. These early observations were followed by multiple reports using either BM-MSCs or AT-MSCs [43,45,48,[90][91][92]. To this end, various protocols were employed.…”

Section: Directed Differentiationmentioning

confidence: 99%

From Mesenchymal Stromal/Stem Cells to Insulin-Producing Cells: Progress and Challenges

Ghoneim

Refaie

Elbassiouny

et al. 2020

Stem Cell Rev and Rep

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Mesenchymal stromal cells (MSCs) are an attractive option for cell therapy for type 1 diabetes mellitus (DM). These cells can be obtained from many sources, but bone marrow and adipose tissue are the most studied. MSCs have distinct advantages since they are nonteratogenic, nonimmunogenic and have immunomodulatory functions. Insulin-producing cells (IPCs) can be generated from MSCs by gene transfection, gene editing or directed differentiation. For directed differentiation, MSCs are usually cultured in a glucose-rich medium with various growth and activation factors. The resulting IPCs can control chemically-induced diabetes in immune-deficient mice. These findings are comparable to those obtained from pluripotent cells. PD-L1 and PD-L2 expression by MSCs is upregulated under inflammatory conditions. Immunomodulation occurs due to the interaction between these ligands and PD-1 receptors on T lymphocytes. If this function is maintained after differentiation, life-long immunosuppression or encapsulation could be avoided. In the clinical setting, two sites can be used for transplantation of IPCs: the subcutaneous tissue and the omentum. A 2-stage procedure is required for the former and a laparoscopic procedure for the latter. For either site, cells should be transplanted within a scaffold, preferably one from fibrin. Several questions remain unanswered. Will the transplanted cells be affected by the antibodies involved in the pathogenesis of type 1 DM? What is the functional longevity of these cells following their transplantation? These issues have to be addressed before clinical translation is attempted.

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Mechanism of insulin production in canine bone marrow derived mesenchymal stem cells

Cited by 9 publications

References 26 publications

Use of Adipose-Derived Mesenchymal Stem Cells in Keratoconjunctivitis Sicca in a Canine Model

Use of Adipose-Derived Mesenchymal Stem Cells in Keratoconjunctivitis Sicca in a Canine Model

Insulin-Producing Cells Differentiated from Human Bone Marrow Mesenchymal Stem Cells In Vitro Ameliorate Streptozotocin-Induced Diabetic Hyperglycemia

From Mesenchymal Stromal/Stem Cells to Insulin-Producing Cells: Progress and Challenges

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