Concise Review: Canine Diabetes Mellitus as a Translational Model for Innovative Regenerative Medicine Approaches

Moshref, Maryam; Tangey, Bonnie; Gilor, Chen; Papas, Klearchos K.; Williamson, Peter; Loomba-Albrecht, Lindsey A.; Sheehy, Paul A.; Kol, Amir

doi:10.1002/sctm.18-0163

Cited by 25 publications

(21 citation statements)

References 49 publications

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“…Current traditional medical treatments have a poor effect in curing numerous dog diseases and injuries, including nerve damage, kidney damage, hepatitis, and diabetes. Therefore, the scientists are constantly exploring new medical tools [14,20,21,22,23]. The emergence of stem cell therapy brings new hope for the treatment of these diseases [24,25].…”

Section: Introductionmentioning

confidence: 99%

A Comparative Study of Biological Characteristics and Transcriptome Profiles of Mesenchymal Stem Cells from Different Canine Tissues

Zhan

El‐Ashram

Luo

et al. 2019

IJMS

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Mesenchymal stem cells (MSCs) are the most promising seed cells for cell therapy. Comparing the biological and transcriptome gene characteristics of MSCs from different sources provides an important basis for the screening of clinically used cells. The main purpose of this experiment was to establish methods for the isolation and culture of MSCs from five different canine sources, including adipose tissue, bone marrow, umbilical cord, amniotic membrane, and placenta, and compare biological and transcriptome characteristics of MSCs, in order to provide a basis for the clinical application of canine MSCs. MSCs were isolated from Chinese pastoral dogs, and the following experiments were performed: (1) the third, sixth, and ninth generations of cells were counted, respectively, and a growth curve was plotted to calculate the MSC population doubling time; (2) the expression of CD34 and CD44 surface markers was studied by immunofluorescence; (3) the third generation of cells were used for osteogenetic and adipogenic differentiation experiments; and (4) MSC transcriptome profiles were performed using RNA sequencing. All of the five types of MSCs showed fibroblast-like adherent growth. The cell surface expressed CD44 instead of CD34; the third-generation MSCs had the highest proliferative activity. The average population doubling time of adipose mesenchymal stem cells (AD-MSCs), placenta mesenchymal stem cells (P-MSCs), bone marrow mesenchymal stem cells (BM-MSCs), umbilical cord mesenchymal stem cells (UC-MSCs), and amniotic mesenchymal stem cells (AM-MSCs) were 15.8 h, 21.2 h, 26.2 h, 35 h, and 41.9 h, respectively. All five types of MSCs could be induced to differentiate into adipocytes and osteoblasts in vitro, with lipid droplets appearing after 8 days and bone formation occurring 5 days after AD-MSC induction. However, the multilineage differentiation for the remaining of MSCs was longer compared to that of the AD-MSCs. The MSC transcriptome profiles showed that AD-MSC and BM-MSCs had the highest homology, while P-MSCs were significantly different compared to the other four types of MSCs. All the isolated MSCs had the main biological characteristics of MSCs. AD-MSCs had the shortest time for proliferation, adipogenesis, and osteogenic differentiation.

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Section: Introductionmentioning

confidence: 99%

A Comparative Study of Biological Characteristics and Transcriptome Profiles of Mesenchymal Stem Cells from Different Canine Tissues

Zhan

El‐Ashram

Luo

et al. 2019

IJMS

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“…Some abnormal expressed genes involved with human diabetes have been identified in dog diabetes cases [ 43 ]. Based on the similar pathology and physiology with human, canine without doubt is an ideal translational disease model for type I diabetes treatment in human [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of the transdifferentiation of canine BMSCs into insulin producing cells

et al. 2021

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Background Bone marrow mesenchymal stem cells are a potential resource for the clinical therapy of certain diseases. Canine, as a companion animal, living in the same space with human, is an ideal new model for human diseases research. Because of the high prevalence of diabetes, alternative transplantation islets resource (i.e. insulin producing cells) for diabetes treatment will be in urgent need, which makes our research on the transdifferentiation of Bone marrow mesenchymal stem cells into insulin producing cells become more important. Result In this study, we completed the transdifferentiation process and achieved the transcriptome profiling of five samples with two biological duplicates, namely, “BMSCs”, “islets”, “stage 1”, “stage 2” and “stage 3”, and the latter three samples were achieved on the second, fifth and eighth day of induction. A total of 11,530 differentially expressed transcripts were revealed in the profiling data. The enrichment analysis of differentially expressed genes revealed several signaling pathways that are essential for regulating proliferation and transdifferentiation, including focal adhesion, ECM-receptor interaction, tight junction, protein digestion and absorption, and the Rap1 signaling pathway. Meanwhile, the obtained protein–protein interaction network and functional identification indicating involvement of three genes, SSTR2, RPS6KA6, and VIP could act as a foundation for further research. Conclusion In conclusion, to the best of our knowledge, this is the first survey of the transdifferentiation of canine BMSCs into insulin-producing cells according with the timeline using next-generation sequencing technology. The three key genes we pick out may regulate decisive genes during the development of transdifferentiation of insulin producing cells.

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“…Some abnormal expressed genes involved with human diabetes have been identi ed in dog diabetes cases [43]. Based on the similar pathology and physiology with human, canine without doubt is an ideal translational disease model for type I diabetes treatment in human [44].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of the Transdifferentiation of canine BMSCs into Insulin Producing Cells

WANG

Dai

Zou

et al. 2020

Preprint

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Background Bone marrow mesenchymal stem cells are a potential resource for the clinical therapy of certain diseases. Canine, as a companion animal, living in the same space with human, is an ideal new model for human diseases research. Because of the high prevalence of diabetes, alternative transplantation islets resource (i.e. insulin producing cells) for diabetes treatment will be in urgent need, which makes our research on the transdifferentiation of Bone marrow mesenchymal stem cells into insulin producing cells become more important.Result In this study, we completed the transdifferentiation process and achieved the transcriptome profiling of five samples with two biological duplicates, namely, “BMSCs”, “islets”, “stage1”, “stage2” and “stage3”, and the latter three samples were achieved on the second, fifth and eighth day of induction. A total of 11,530 differentially expressed transcripts were revealed in the profiling data. The enrichment analysis of differentially expressed genes revealed several signaling pathways that are essential for regulating proliferation and transdifferentiation, including focal adhesion, ECM–receptor interaction, tight junction, protein digestion and absorption, and the Rap1 signaling pathway. Meanwhile, the obtained protein–protein interaction network and functional identification indicating involvement of three genes, SSTR2, RPS6KA6, and VIP could act as a foundation for further research.Conclusion In conclusion, to the best of our knowledge, this is the first survey of the transdifferentiation of canine BMSCs into insulin-producing cells according with the timeline using next-generation sequencing technology. The three key genes we pick out may regulate decisive genes during the development of transdifferentiation.

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Concise Review: Canine Diabetes Mellitus as a Translational Model for Innovative Regenerative Medicine Approaches

Cited by 25 publications

References 49 publications

A Comparative Study of Biological Characteristics and Transcriptome Profiles of Mesenchymal Stem Cells from Different Canine Tissues

A Comparative Study of Biological Characteristics and Transcriptome Profiles of Mesenchymal Stem Cells from Different Canine Tissues

Transcriptome analysis of the transdifferentiation of canine BMSCs into insulin producing cells

Transcriptome Analysis of the Transdifferentiation of canine BMSCs into Insulin Producing Cells

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