Fibronectin and pellet suspension culture promote differentiation of human mesenchymal stem cells into insulin producing cells

Chang, Che Shoa; Hsu, Ke Hsun; Chiou, Shih Hwa; Ho, Larry Low Tone; Fu, Yu; Hung, Shih Chieh

doi:10.1002/jbm.a.31767

Cited by 30 publications

(21 citation statements)

References 28 publications

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“…Gao et al (2008) have indicated that extracellular matrix gel plays an important role not only in differentiation of human umbilical cord blood derived MSCs into IPCs, but also in maturation and formation of three dimensional structures. This observations were confirmed by other authors (Chang et al 2008). …”

Section: Differentiation Of Other Types Of Mscssupporting

confidence: 91%

Differentiation of Stem Cells into Insulin-Producing Cells: Current Status and Challenges

Pokrywczyńska

Krzyzanowska

Jundziłł

et al. 2013

Arch. Immunol. Ther. Exp.

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Diabetes mellitus is one of the most serious public health challenges of the twenty-first century. Allogenic islet transplantation is an efficient therapy for type 1 diabetes. However, immune rejection, side effects of immunosuppressive treatment as well as lack of sufficient donor organs limits its potential. In recent years, several promising approaches for generation of new pancreatic b cells have been developed. This review provides an overview of current status of pancreatic and extra-pancreatic stem cells differentiation into insulin-producing cells and the possible application of these cells for diabetes treatment. The PubMed database was searched for English language articles published between 2001 and 2012, using the keyword combinations: diabetes mellitus, differentiation, insulin-producing cells, stem cells.

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Section: Differentiation Of Other Types Of Mscssupporting

confidence: 91%

Differentiation of Stem Cells into Insulin-Producing Cells: Current Status and Challenges

Pokrywczyńska

Krzyzanowska

Jundziłł

et al. 2013

Arch. Immunol. Ther. Exp.

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“…Cells in cell clusters, affected by surrounding cells via paracrine, easily coordinated each other and differentiated. Chang and colleagues showed that human BMSCs centrifuged into cell pellets more easily differentiated towards IPCs than those under a monolayer [8]. Studies have shown that cell–cell contact between pancreatic beta-cells is important for maintaining their survival and increasing insulin secretion [24].…”

Section: Discussionmentioning

confidence: 99%

Under a nonadherent state, bone marrow mesenchymal stem cells can be efficiently induced into functional islet-like cell clusters to normalize hyperglycemia in mice: a control study

Zhang¹,

Dou²

2014

Stem Cell Res Ther

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IntroductionBone marrow mesenchymal stem cells (BMSCs) possess low immunogenicity and immunosuppression as an allograft, can differentiate into insulin-producing cells (IPCs) by in vitro induction, and may be a valuable cell source to regenerate pancreatic islets. However, the very low differentiation efficiency of BMSCs towards IPCs under adherent induction has thus far hindered the clinical exploitation of these cells. The aim of this study is to explore a new way to efficiently induce BMSCs into IPCs and lay the groundwork for their clinical exploitation.MethodsIn comparison with adherent induction, BMSCs of human first-trimester abortus (hfBMSCs) under a nonadherent state were induced towards IPCs in noncoated plastic dishes using a three-stage induction procedure developed by the authors. Induction effects were evaluated by statistics of the cell clustering rate of induced cells, and ultrastructural observation, dithizone staining, quantitative polymerase chain reaction and immunofluorescence assay, insulin and c-peptide release under glucose stimulus of cell clusters, as well as transplantation test of the cell clusters in diabetic model mice.ResultsWith (6.175 ± 0.263) × 105 cells in 508.5 ± 24.5 cell clusters, (3.303 ± 0.331) × 105 single cells and (9.478 ± 0.208) × 105 total cell count on average, 65.08 ± 2.98% hfBMSCs differentiated into pancreatic islet-like cell clusters after nonadherent induction. With (3.993 ± 0.344) × 105 cells in 332.3 ± 41.6 cell clusters, (5.437 ± 0.434) × 105 single cells and (9.430 ± 0.340) × 105 total cell count on average, 42.37 ± 3.70% hfBMSCs differentiated into pancreatic islet-like cell clusters after adherent induction (P < 0.01, n = 10). The former is significantly higher than the latter. Calculated according to the cell clustering rate and IPC percentage in the cell clusters, 29.80 ± 3.95% hfBMSCs differentiated into IPCs after nonadherent induction and 18.40 ± 2.08% hfBMSCs differentiated into IPCs after adherent induction (P < 0.01, n = 10), the former significantly higher than the latter. The cell clusters expressed a broad gene profile related to pancreatic islet cells, released insulin and c-peptide in a glucose concentration-dependent manner, and normalized hyperglycemia of streptozocin-induced mice for at least 80 days following xenograft. Blood glucose of grafted mice rose again after their graft removed. A series of examination of the grafts showed that transplanted cells produced human insulin in recipients.ConclusionsOur studies demonstrate that nonadherent induction can greatly promote BMSCs to form pancreatic islet-like cell clusters, thereby improving the differentiation efficiency of BMSCs towards IPCs.

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“…Their directed differentiation and subsequent transplantation has met only with partial success in preclinical models (66)(67)(68)(69)(70)(71)(72)(73)(74)(75). However, when directly infused in an undifferentiated state onto diabetic subjects, a variable degree of endogenous regeneration has been observed (76)(77)(78)(79). It is now broadly believed that MSCs are at their therapeutic best when used in this context, probably due to their wellstudied immunomodulatory, anti-inflammatory, proangiogenic, and trophic properties (80)(81)(82)(83)(84)(85)(86)(87).…”

Section: Adult Stem Cellsmentioning

confidence: 99%

Cell Replacement Strategies Aimed at Reconstitution of the β-Cell Compartment in Type 1 Diabetes

et al. 2014

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Emerging technologies in regenerative medicine have the potential to restore the b-cell compartment in diabetic patients, thereby overcoming the inadequacies of current treatment strategies and organ supply. Novel approaches include: 1) Encapsulation technology that protects islet transplants from host immune surveillance; 2) stem cell therapies and cellular reprogramming, which seek to regenerate the depleted b-cell compartment; and 3) whole-organ bioengineering, which capitalizes on the innate properties of the pancreas extracellular matrix to drive cellular repopulation. Collaborative efforts across these subfields of regenerative medicine seek to ultimately produce a bioengineered pancreas capable of restoring endocrine function in patients with insulin-dependent diabetes.Regenerative medicine promises to contribute to the advancement of b-cell replacement strategies through the development and implementation of microencapsulation technology, the production of insulin-producing cells either by regeneration from endogenous cells or reprogramming from nonendocrine adult cell sources, and, more recently, the exploitation of bioengineered microenvironments (1). Considering the shortage of available pancreata, the search for alternative cell sources has recently been categorized within one of the following three "Rs" of pancreatic b-cell replenishment: replacement (from stem cells or xenoislets), regeneration (from endogenous progenitor cells), and reprogramming (from nonendocrine adult cell sources) (2).The purpose of this article is to comprehensively and critically review the main regenerative medicine2based strategies that are currently being developed to treat type 1 diabetes. The first part of the article will illustrate and discuss islet encapsulation technology, which has been extensively investigated over the past 40 years (3) and represents one of the most promising regenerative medicine2based approaches to achieve immunoisolation of transplantable organs. The second part will focus on cell bioengineering, where different types of progenitor and differentiated cell sources are manipulated to ultimately yield insulin-producing cells. The last part of the article will summarize the most recent advancements in the study of the pancreatic extracellular matrix (ECM) as a platform for endocrine pancreas bioengineering. ISLET ENCAPSULATION TECHNOLOGYEncapsulation technology has been used to protect islets from the host immune system. This strategy holds the promise to allow implantation of islets without immunosuppression not only across genetically different individuals from the same species, but also across species barriers. MicroencapsulationThe first approach to immunoisolate cells consists of the microencapsulation of one to three islets per semipermeable immunoprotective capsule. The spherical configuration of these microcapsules results in a higher surface-tovolume ratio and a higher diffusion rate (4). Furthermore, microcapsules can be injected in large numbers, are durable, and are difficult to disrup...

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Fibronectin and pellet suspension culture promote differentiation of human mesenchymal stem cells into insulin producing cells

Cited by 30 publications

References 28 publications

Differentiation of Stem Cells into Insulin-Producing Cells: Current Status and Challenges

Differentiation of Stem Cells into Insulin-Producing Cells: Current Status and Challenges

Under a nonadherent state, bone marrow mesenchymal stem cells can be efficiently induced into functional islet-like cell clusters to normalize hyperglycemia in mice: a control study

Cell Replacement Strategies Aimed at Reconstitution of the β-Cell Compartment in Type 1 Diabetes

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