Mesenchymal Stem Cells Adopt β-Cell Fate Upon Diabetic Pancreatic Microenvironment

Chang, Caihong; Wang, Xinjun; Deliang, Niu; Zhang, Zhan; Zhao, Hongyang; Gong, Feili

doi:10.1097/mpa.0b013e318191521c

Cited by 21 publications

(13 citation statements)

References 28 publications

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“…[39][40][41] A few studies have injected MSCs into diabetic mice or pigs and demonstrated a reduction in blood glucose, though this appears to be due more to a regeneration of host b-cell mass rather than differentiation of MSCs into b-cells. 42,43 b-Cell regeneration is believed to be due to the immunomodulatory and angiogenic effects of MSCs, though the exact mechanism is not known. 44 The most widely adopted use of MSCs is in coculture with implanted islets, which has been shown to improve the clinical outcome by revascularizing the transplant and protecting the islets from immune attack.…”

Section: Stem Cellsmentioning

confidence: 99%

Tissue Engineering Approaches to Cell-Based Type 1 Diabetes Therapy

Amer

Mahoney

Bryant

2014

Tissue Engineering Part B: Reviews

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Type 1 diabetes mellitus is an autoimmune disease resulting from the destruction of insulin-producing pancreatic b-cells. Cell-based therapies, involving the transplantation of functional b-cells into diabetic patients, have been explored as a potential long-term treatment for this condition; however, success is limited. A tissue engineering approach of culturing insulin-producing cells with extracellular matrix (ECM) molecules in threedimensional (3D) constructs has the potential to enhance the efficacy of cell-based therapies for diabetes. When cultured in 3D environments, insulin-producing cells are often more viable and secrete more insulin than those in two dimensions. The addition of ECM molecules to the culture environments, depending on the specific type of molecule, can further enhance the viability and insulin secretion. This review addresses the different cell sources that can be utilized as b-cell replacements, the essential ECM molecules for the survival of these cells, and the 3D culture techniques that have been used to benefit cell function.

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Section: Stem Cellsmentioning

confidence: 99%

Tissue Engineering Approaches to Cell-Based Type 1 Diabetes Therapy

Amer

Mahoney

Bryant

2014

Tissue Engineering Part B: Reviews

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“…In experimental studies, the process of regeneration followed an operative insult involving the removal of a part of the organ [23]. 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].…”

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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“…В нескольких исследованиях после введения МСК диабетическим мышам наблюдали снижение уровня глюкозы в крови, хотя это, по-видимому, обусловлено регенерацией пула β-клеток реципи-ента, а не дифференцировкой МСК в β-клетки [35,36]. Регенерация β-клеток, как полагают, происхо-дит вследствие иммуномодулирующего и ангиоген-ного эффектов МСК, хотя точный механизм неиз-вестен [37].…”

Section: мезенхимальные стволовые клеткиunclassified

Prospects of Application of Tissue-Engineered Pancreatic Constructs in the Treatment of Type 1 Diabetes

Skaletskaya

Skaletskiy

Sevastianov

2017

RJTAO

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ФГБУ «Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России, Москва, Российская Федерация Наиболее эффективным методом лечения сахарного диабета 1-го типа по-прежнему является аллотранс-плантация островков поджелудочной железы, которая при сочетании благоприятных условий (достаточ-ное количество выделенных островков, удачная комбинация иммуносупрессивных препаратов) способна достичь инсулиннезависимости реципиентов на протяжении нескольких лет. Однако постоянный дефи-цит донорских поджелудочных желез и ограниченность выживания островков в организме реципиента не позволяют увеличить количество таких трансплантаций и повысить их эффективность. В настоящем обзоре дан критический анализ работ российских и зарубежных авторов по созданию тканеинженерных конструкций поджелудочной железы, направленных на решение трех главных проблем трансплантации островков поджелудочной железы: 1) дефицит донорского материала; 2) необходимость проведения им-муносупрессивной терапии; 3) непродолжительность выживания и функциональной активности переса-женных островков.Ключевые слова: сахарный диабет 1-го типа, трансплантация, островки, поджелудочная железа, тканеинженерные конструкции. Allotransplantation of pancreatic islets remains the most effective method of treatment of diabetes mellitus type 1 being capable under combination of favorable conditions (suffi cient number of isolated islets, effective combination of immunosuppressive drugs) to reach the recipients' insulin independence for several years. However, the overwhelming shortage of donor pancreas and limited post-transplantation islet survival do not allow increasing the number of such transplants and their effectiveness. This review presents a critical analysis of the work done by Russian and foreign authors onto creation of tissue-engineered pancreatic constructs that may lead to the resolution of the three main pancreatic islet transplantation issues: 1) lack of donor material; 2) necessity of immunosuppressive therapy; 3) limited survival and functional activity of the islet. PROSPECTS OF APPLICATION OF TISSUE-ENGINEERED PANCREATIC CONSTRUCTS IN THE TREATMENT Key words: diabetes mellitus type 1, transplantation, islets, pancreas, tissue-engineered constructs.Для корреспонденции: Скалецкий Николай Николаевич. Адрес: 123182, Москва, ул. Щукинская, д. 1. В настоящее время золотым стандартом лечения сахарного диабета 1-го типа по-прежнему является введение экзогенного инсулина в ответ на повышен-ный уровень глюкозы в крови. Создание синтети-ческих аналогов инсулина, их введение с помощью носимых дозаторов, возможность регулярного кон-

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Mesenchymal Stem Cells Adopt β-Cell Fate Upon Diabetic Pancreatic Microenvironment

Abstract: This study shows that MSCs could adopt beta-cell fate in diabetic pancreatic microenvironment without obvious immune rejections. Stem cell transplantation in orthotope is a promising therapy for diabetes.

Cited by 21 publications

References 28 publications

Tissue Engineering Approaches to Cell-Based Type 1 Diabetes Therapy

Tissue Engineering Approaches to Cell-Based Type 1 Diabetes Therapy

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

Prospects of Application of Tissue-Engineered Pancreatic Constructs in the Treatment of Type 1 Diabetes

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