scholarly journals Pancreatic Lineage Cell Differentiation of Bone Marrow Mesenchymal Stromal Cells on Acellular Pancreatic Bioscaffold

2020 ◽  
Author(s):  
Zhao Li ◽  
Yue Du ◽  
Xin Wang
Keyword(s):  
Electron Microscopy ◽  
Cell Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Pancreatic Tissue ◽  
In Vivo Study ◽  
Morphological Observation ◽  
Collagen Types ◽  
Pancreatic Cell

Abstract Background:We evaluated(1) the potential differentiation ability of bone mesenchymal stromal cells(BMSCs) into pancreatic lineage cells on rat acellular pancreatic bioscaffold (APB) and (2) the effect of differentiated BMSCs on chronic pancreatitis in vivo.Methods:After BMSCs were isolated and characterized, they were dynamically cultured on APB and statically cultured in tissue culture flasks (TCFs), with or without growth factor(GF) in both culture systems. We assessed cytological behavior, such as the proliferation and differentiation of BMSCs, by morphological observation, flow cytometry, enzyme-linked immunosorbent assay (ELISA), quantitative real-time/reverse transcriptase polymerase chain reaction, and Western blot analysis. For the in vivo study, we evaluated the pancreatic fibrosis and pathological scores.We detected the expression of α-SMA,collagen types I and III,and IL-10 in pancreatic tissue by ELISA.Results:The most appropriate flow rate for the dynamic culture of BMSCs was 4mL/min. The proliferation rates of BMSCs in the APB groups were significantly higher than in the TCF groups.During the pancreatic lineage cell differentiation process, APB induced BMSCs to express mRNA markers such as PDX-1 and PTF-1 at higher levels. In contrast, the marker Oct4 was expressed at a lower level in the APB group. All tested pancreatic cytokeratins, including α-Amy, CK7, Flk-1, and C-peptide, were expressed at higher levels in the APB group. The secretion of metabolic enzymes, such as Amy and insulin, was higher in the APB system. By scanning electron microscopy and transmission electron microscopy, the ultrastructure of BMSCs in the APB group further revealed the morphological characteristics of pancreatic-like cells. In the in vivo study, the expression of α-SMA and collagen types I and III in tissues was significantly lower in differentiated BMSCs group, whereas the levels of IL-10 in pancreatic tissue were higher in differentiated BMSCs with significant difference. In addition, in both the in vitro and the in vivo study, GF significantly improved proliferation, differentiation, and pancreatic cell therapy.Conclusion: Our data showed (1) the capacity of APB, a three-dimensional pancreatic biomatrix, to promote BMSC differentiation toward pancreatic lineage and pancreatic-like phenotypes, and (2) the considerable potential of using these cells for pancreatic cell therapies and tissue engineering.

scholarly journals Pancreaticline Cell Differentiation of Bone Marrow Mesenchymal Stromal Cells in Acellular Pancreatic Scaffolds

2020 ◽  
Author(s):  
Zhao Li ◽  
Yue Du ◽  
Xin Wang
Keyword(s):  
Cell Differentiation ◽  
Treatment Group ◽  
Stromal Cells ◽  
Culture System ◽  
Collagen Type ◽  
Collagen Type I ◽  
In Vivo Study ◽  
Type I ◽  
Pancreatic Cell

Abstract Background: To evaluate the potential differentiation ability of bone mesenchymal stromal cells(BMSCs) to pancreatic line Cells on rat acellular pancreatic bioscaffold(APB) and the effect of differentiated BMSCs for chronic pancreatitis(CP) in vivo. Methods: After BMSCs were isolated and identified, they were dynamic cultured on the APB and static cultured in tissue culture flask(TCF),with or without the growth factors (GF) in both the culture system. The cytological behavior such as the proliferation and differentiation of BMSCs in all the above kinds of culture system were assessed by morphological observation, flow cytometry, ELASA analysis, qRT-PCR assay and western blot analysis. For the in vivo study, the pancreatic fibrosis and pathological score were evaluated. And also the expression of α-SMA, collagen type I and III, IL-10 in pancreas tissue were detected by ELASA. Results: 4ml/min was the most appropriate flow rate for the dynamic culture of BMSCs. The proliferation rate of BMSCs in the APB groups were significantly increased compared to TCF system. During the pancreatic line cell differentiation process, APB could induce BMSCs express markers such as PDX-1 and PTF-1 at higher mRNA levels. In contrast, the marker Oct 4 was expressed at a lower level in APB group. For the pancreatic functional cytoketatins including α-Amy, CK7, Flk-1, and C-peptide, they were all expressed at higher level in APB group. And metabolic enzymes secretion such as amylase and insulin were promoted significantly in APB system. By scanning electron microscope(SEM) and transmission electron microscopy(TEM), the ultrastructure of BMSCs in the APB group could further demonstrated the morphological characteristics of pancreatic-like cells. In vivo study,the expression of α-SMA, collagen type I and III in tissues were less in differentiated BMSCs treatment group, while the level of IL-10 in pancreatic tissue were higher in differentiated BMSCs treatment group with significant difference (P<0.05). In addition, in both in vitro and in vivo study, GF could significantly facilitate the function of proliferation, differentiation and pancreatic cell therapy. Conclusion: Together our data show the capacity of APB , 3D pancreatic biomatrix, promoting BMSCs differentiate toward pancreatic line phenotypes, and the considerable potential of using these cells for pancreatic cell therapies and tissue engineering.

scholarly journals Pancreatic line Cell Differentiation of bone marrow Mesenchymal Stromal Cells in Acellular Pancreatic Scaffolds

2020 ◽  
Author(s):  
Zhao Li ◽  
Yue Du ◽  
Xin Wang
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Flow Rate ◽  
Stromal Cells ◽  
Culture System ◽  
Morphological Observation ◽  
Static System ◽  
Mrna Levels ◽  
Dynamic Culture

Abstract Background: To evaluate the potential differentiation ability of bone mesenchymal stromal cells(BMSCs) to pancreatic line Cells on rat acellular pancreatic bioscaffold (APB). Methods: Fresh pancreata from 20 Adult Sprague Dawley rats (between 6 and 7 weeks old) were soaked and perfused using Easy-Load Digital Drive peristaltic pumps. After BMSCs were isolated and identified, they were dynamic cultured on the APB and static cultured in tissue culture flask(TCF). Based on whether the differentiation was induced by the growth factors (GF) in the culture system, our study was divided into 4 groups: BMSCs cultured in TCF without any GF(TCF-GF(-)), BMSCs cultured in TCF with GF(TCF-GF(+)), BMSCs cultured on APB without GF(APB-GF(-)), BMSCs cultured on APB with GF (APB-GF(+)).The cytological behavior such as the proliferation and differentiation of BMSCs in all the above kinds of culture system with or without GF were assessed by morphological observation, flow cytometry, ELASA analysis, qRT-PCR assay and western blot analysis. Results: 4ml/min was the most appropriate flow rate for the dynamic culture of BMSCs. Under culture conditions, BMSCs populations could attach to and proliferate within the APB. APB could promote the proliferation and viability of BMSCs significantly better in dynamic culture with optimal flow rate 4ml/min, when compared to the static culture system. Also, the proliferation rate of BMSCs in the APB groups were significantly increased compared to TCF system. During the pancreatic line cell differentiation process, APB could induce BMSCs into pancreatic-like cells which expressed markers such as pancreatic duodenal homeodomain containing transcription factor (PDX-1) and pancreatic exocrine transcription factor (PTF-1) higher at mRNA levels compared to TCF system. In contrast, the marker Oct4 (octamer-binding transcription factor 4) was expressed at a lower level in APB group. For the pancreatic functional cytoketatins including α-Amylase(α-Amy), cytokeratin 7(CK7), fetal liver kinase-1 (Flk-1),and C-peptide, they were all expressed at higher level in APB group than in the TCF group. And metabolic enzymes secretion such as amylase and insulin were promoted significantly in APB system. By scanning electron microscope(SEM) and transmission electron microscopy(TEM), the ultrastructure of BMSCs in the APB group could further demonstrated the morphological characteristics of pancreatic-like cells. In addition, in both the dynamic and static system, GF could significantly facilitate the function of proliferation, differentiation and cell engraftment . Conclusion: Together our data show the capacity of APB , 3D pancreatic biomatrix, promoting BMSCs differentiate toward pancreatic line phenotypes, and the considerable potential of using these cells for pancreatic cell therapies and tissue engineering.

scholarly journals Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review

2021 ◽  
Vol 10 (13) ◽  
pp. 2925
Author(s):  
Manuel Sanchez-Diaz ◽  
Maria I. Quiñones-Vico ◽  
Raquel Sanabria de la Torre ◽  
Trinidad Montero-Vílchez ◽  
Alvaro Sierra-Sánchez ◽  
...  
Keyword(s):  
Animal Models ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cellular Therapy ◽  
The Body ◽  
Intralesional Injection ◽  
Intraarterial Infusion ◽  
Routes Of Administration ◽  
Administration Routes

Mesenchymal Stromal Cells (MSCs) are of great interest in cellular therapy. Different routes of administration of MSCs have been described both in pre-clinical and clinical reports. Knowledge about the fate of the administered cells is critical for developing MSC-based therapies. The aim of this review is to describe how MSCs are distributed after injection, using different administration routes in animal models and humans. A literature search was performed in order to consider how MSCs distribute after intravenous, intraarterial, intramuscular, intraarticular and intralesional injection into both animal models and humans. Studies addressing the biodistribution of MSCs in “in vivo” animal models and humans were included. After the search, 109 articles were included in the review. Intravenous administration of MSCs is widely used; it leads to an initial accumulation of cells in the lungs with later redistribution to the liver, spleen and kidneys. Intraarterial infusion bypasses the lungs, so MSCs distribute widely throughout the rest of the body. Intramuscular, intraarticular and intradermal administration lack systemic biodistribution. Injection into various specific organs is also described. Biodistribution of MSCs in animal models and humans appears to be similar and depends on the route of administration. More studies with standardized protocols of MSC administration could be useful in order to make results homogeneous and more comparable.

scholarly journals Evaluation of Browning Agents on the White Adipogenesis of Bone Marrow Mesenchymal Stromal Cells: A Contribution to Fighting Obesity

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 403
Author(s):  
Girolamo Di Maio ◽  
Nicola Alessio ◽  
Ibrahim Halil Demirsoy ◽  
Gianfranco Peluso ◽  
Silverio Perrotta ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
White Adipocyte ◽  
Drug Candidates ◽  
Fat Depots ◽  
Treatment Of Obesity ◽  
White Fat

Brown-like adipocytes can be induced in white fat depots by a different environmental or drug stimuli, known as “browning” or “beiging”. These brite adipocytes express thermogenin UCP1 protein and show different metabolic advantages, such as the ability to acquire a thermogenic phenotype corresponding to standard brown adipocytes that counteracts obesity. In this research, we evaluated the effects of several browning agents during white adipocyte differentiation of bone marrow-derived mesenchymal stromal cells (MSCs). Our in vitro findings identified two compounds that may warrant further in vivo investigation as possible anti-obesity drugs. We found that rosiglitazone and sildenafil are the most promising drug candidates for a browning treatment of obesity. These drugs are already available on the market for treating diabetes and erectile dysfunction, respectively. Thus, their off-label use may be contemplated, but it must be emphasized that some severe side effects are associated with use of these drugs.

scholarly journals Equine allogeneic bone marrow-derived mesenchymal stromal cells elicit antibody responses in vivo

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Lynn M Pezzanite ◽  
Lisa A Fortier ◽  
Douglas F Antczak ◽  
Jennifer M Cassano ◽  
Margaret M Brosnahan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Allogeneic Bone Marrow ◽  
Antibody Responses ◽  
Allogeneic Bone
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