Human Bone Marrow Subpopulations Sustain Human Islet Function and Viability In vitro
Journal Title: Journal of Advances in Medicine and Medical Research - Year 2015, Vol 8, Issue 7
Abstract
Aims: Allogeneic bone marrow (BM) has been shown to support human islet survival and function in long-term culture by initiating human islet vascularization and β-cell regeneration. Various BM subpopulations may play different roles in human islet functions and survival. In this paper we investigated the effects of BM and its subpopulations, endothelial progenitor cells (E) and mesenchymal (M) cells on human islet’s β-cell function and regeneration. Study Design: Isolation and identification of subpopulations from human bone marrow and culture with allogeneic human islet to investigate effects of different cell population on human islet function and regeneration. Place and Duration of Study: Department of Medicine, Center for Stem Cell & Diabetes Research, RWMC, Providence, RI, USA, between 2010 - 2014. Methodology: Human islets were distributed from Integrated Islet Distribution Program (IIDP) and human bone marrow (BM) was harvested by Bone marrow transplantation center at Roger Williams Hospital. BM subpopulation was identified cell surface markers through Fluorescence-activated cell sorting, applied in flow cytometry (FACS), islet function was evaluated by human ELISA kit and β cell regeneration was evaluated by three methods of Cre-Loxp cell tracing, β cell sorting and RT-PCR for gene expression. Results: Four different BM and seven different islet donates contributed human tissues. We observed islet β-cell having self regeneration capability in short term culture (3~5 days) using a Cre-Loxp cell tracing. BM and its subtype E, M have similar benefits on β cell function during co-culture with human islet comparison to islet only. However, only whole BM enables to sustain the capability of islet β-cell self regeneration resulting in increasing β cell population while single E and M individual do not significantly affect on that. Mechanism approach to explore β-cell self regeneration by evaluating transcription factor expressions, we found that BM significantly increases the activations of β-cell regeneration relative transcription factors, the LIM homeodomain protein (Isl1), homologue to zebrafish somite MAF1 (MAFa), the NK-homeodomain factor 6.1 (NKX6.1), the paired box family factors 6 (PAX6), insulin promoter factor 1 (IPF1) and kinesin family member 4A (KIF4a). Conclusion: These results suggest that BM and its derived M and E cells enable to support human islet β-cell function. However, only BM can sustain the capability of β-cell self regeneration through initiating β-cell transcriptional factors but not individual E and M cells suggesting pure E and M cells less supportive for islet long-term survival in vitro.
Authors and Affiliations
Lu Guang Luo, Fang Xiong, Philippe Ravassard, John ZQ Luo
Keywords
Related Articles
- EP ID EP347384
- DOI 10.9734/BJMMR/2015/17536
- Views 50
- Downloads 0
Spontaneous Twin Ectopic Pregnancy with Live Embryos: A Case Report
Ectopic pregnancy is a challenging medical emergency that can be easily misdiagnosed. Early diagnosis is essential in ectopic pregnancy since it may be a life-threatening clinical entity if it is misdiagnosed and rupture...
Delayed Presentation of Bone and Soft Tissue Sarcoma of the Extremity in Makurdi: Do Traditional Bone Setters Play a Role?
Background: Soft tissue and bone sarcomas are rare but are associated with high mortality rate when they occur. This is partly due to delay in presentation to a specialist center .Some guidelines have been introduced to...
Significant ACE Gene Haplotype Stipulates Development of Type 2 Diabetes in Women with Gestational Diabetes Mellitus
Introduction: Angiotensin-converting enzyme (ACE) plays a key role in glucose and insulin regulation, and in the onset of diabetes. ACE gene polymorphisms A240T, C1237T, G2350A and I/D located in the promoter, coding and...
Malarial Acute Kidney Injury: 25 Years Experience from a Center in an Endemic Region
Background: While malaria rarely occurs in many parts of the world, it still causes serious complications like acute kidney injury (AKI) in endemic areas and needs to be reported. Methods: This study was carried out at S...
Chest Radiographic Patterns of Smear Positive Tuberculosis in Relation to HIV: A Cross-Sectional Study in a Population with a High Burden of HIV and Tuberculosis
Aim: The purpose of this study was to investigate the chest radiographic patterns of smear positive pulmonary tuberculosis patients in relation to HIV co-infection. Study Deign: Cross-sectional descriptive study Place a...