Effects of Intrahepatic Bone-Derived Mesenchymal Stem Cells Autotransplantation on the Diabetic Beagle Dogs

Zhu, Shajun; Lu, Yao; Zhu, Jianwei; Xu, Jian; Huang, Hua; Zhu, Mingyan; Chen, Yuquan; Zhou, Yuan; Fan, Xiangjun; Wang, Zhiwei

doi:10.1016/j.jss.2009.10.008

Cited by 29 publications

(17 citation statements)

References 41 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A previous study demonstrated that atherosclerosis and vascular inflammation were decreased in homozygous Egr-1 -/-/ apoE -/-double-knockout mice [19]. Stem cell therapy has recently shown promise in the prevention of diabetic complications due to its regenerative potential [20][21][22]. However, it has been demonstrated that diabetic adipose tissue-derived mesenchymal stem cells (dAT-MSCs) had abnormal gene expression profiles and exhibited a low capacity for differentiation into osteoblasts and chondrocytes in comparison to non-diabetic adipose tissue-derived mesenchymal stem cells (nAT-MSCs) under in vitro conditions that mimicked hyperglycemia [23].…”

Section: Introductionmentioning

confidence: 99%

Increased Expression of EGR-1 in Diabetic Human Adipose Tissue-Derived Mesenchymal Stem Cells Reduces Their Wound Healing Capacity

Trinh

Yamashita

Ohneda

et al. 2016

Stem Cells and Development

View full text Add to dashboard Cite

The prevalence of type 2 diabetes mellitus (T2DM), which leads to diabetic complications, has been increasing worldwide. The possible applications of T2DM-derived stem cells in cell therapy are limited because their characteristics are still not fully understood. In this study, we characterized adipose tissue-derived mesenchymal stem cells (AT-MSCs) from diabetic patients (dAT-MSCs) and found that insulin receptor substrate-1 (IRS-1) was highly phosphorylated at serine 636/639 in dAT-MSCs. Moreover, we found that early growth response factor-1 (EGR-1) and its target genes of PTEN and GGPS1 were highly expressed in dAT-MSCs in comparison to healthy donor-derived AT-MSCs (nAT-MSCs). We observed impaired wound healing after the injection of dAT-MSCs in the ischemic flap mouse model. The expressions of EGR-1 and its target genes were diminished by small hairpin RNA-targeted EGR-1 (shEGR-1) and treatment with a mitogen-activated protein kinase/extracellular signalregulated kinase (MAPK/ERK) inhibitor (PD98059). Importantly, dAT-MSCs with shEGR-1 were able to restore the wound healing ability in the mouse model. Interestingly, under hypoxic conditions, hypoxia-inducible factor1a (HIF-1a) can bind to the EGR-1 promoter in dAT-MSCs, but not in nAT-MSCs. Together, these results demonstrate that the expression of EGR-1 was upregulated in dAT-MSCs through two pathways: the main regulatory pathway is the MAPK/ERK pathway, the other is mediated by HIF-1a through direct transcriptional activation at the promoter region of the EGR1 gene. Our study suggests that dAT-MSCs may contribute to microvascular damage and delay wound healing through the overexpression of EGR-1. Interrupting the expression of EGR-1 in dAT-MSCs may be a useful treatment for chronic wounds in diabetic patients.

show abstract

Section: Introductionmentioning

confidence: 99%

Increased Expression of EGR-1 in Diabetic Human Adipose Tissue-Derived Mesenchymal Stem Cells Reduces Their Wound Healing Capacity

Trinh

Yamashita

Ohneda

et al. 2016

Stem Cells and Development

View full text Add to dashboard Cite

show abstract

“…About 0.2–2 % of cats in the United States suffer from diabetes mellitus, lymphoma or retinal disease [13–16]which also affect considerable numbers of other species, including humans [17–19]. There are reports of cell-based therapies for these conditions in humans and animals [17–21], but, to date, information surrounding comparable therapies for the conditions in cats is scarce.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Doses of Multipotent Stromal Cells from Minimal Adipose Tissue

Zhang

Dietrich

Lopez

2014

Stem Cell Rev and Rep

View full text Add to dashboard Cite

Low yield of adult adipose-derived multipotent stromal cells (ASC) can limit autologous cell therapy in individuals with minimal adipose tissue. In this study, ASC isolation was optimized from approximately 0.2 g of feline epididymal adipose tissue for a treatment dose of 106–107 ASCs/kg. The ASC yield was determined for three digestions, 0.1 % collagenase in medium for 30 min (Classic), 0.3 % collagenase in buffer for 30 min (New) and 0.3 % collagenase in buffer for 1 h (Hour). After isolation by the new tissue digestion, continuously cultured ASCs (fresh) and cells recovered and expanded after cryostorage at P0 (revitalized) were characterized up to cell passage (P) 5. Outcomes included CD9, CD29, CD44, CD90 and CD105 expression, cell doublings and doubling times, fibroblastic, adipogenic and osteogenic colony forming unit (CFU) frequency percentages and lineage-specific target gene expression after induction. The New digestion had the highest CFU yield, and about 7x106 ASCs/kg were available within three cell passages (P2). Compared to earlier passages, target surface antigen expression was lowest in fresh P5 cells, and fresh and revitalized P3–5 cells had slower expansion. Fresh and revitalized P1 ASCs had higher CFU frequency percentages and lineage-specific gene expression than P3. The New method described in this study was most efficient for feline epididymal ASC isolation and did not alter in vitro cell behavior. Fresh and revitalized P0-P2 feline ASCs may be most effective for preclinical and clinical trials. This study offers a potential option for ASC isolation from limited adipose tissue resources across species.

show abstract

“…Experimental and clinical stem cell trials on various diseases such as diabetes, arthritis, and spinal cord injury have been increased in the veterinary field using MSCs (Minguell et al 2010;Fortier and Travis 2011;Lee et al 2011;Zhu et al 2011). Recently, some benefit and therapeutic effects of adipose tissue derived-MSC (Ad-MSC) from the dog have been reported (Neupane et al 2008;Vieira et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus After Intrathecal Treatment with Adipose-Derived Mesenchymal Stem Cells

et al. 2011

View full text Add to dashboard Cite

Mesenchymal stem cells (MSC) have emerged as a new therapeutic tool for a number of clinical applications, because they have multipotency and paracrine effects via various factors. In the present study, we investigated the effects of adipose-derived MSC (Ad-MSC) transplantation via intrathecal injection through the cisterna magna on cell proliferation and differentiation of endogenous stem cells in the hippocampal dentate gyrus (DG) using Ki-67 (a marker for proliferating cells), and doublecortin (DCX, a marker for neuroblasts). The transplanted Ad-MSC were detected in the meninges, not in the hippocampal parenchyma. However, the number of Ki-67-immunoreactive cells was significantly increased by 83% in the DG 2 days after single Ad-MSC injection, and by 67% at 23 days after repeated Ad-MSC treatment compared with that in the vehicle-treated group after Ad-MSC transplantation. On the other hand, the number of DCX-immunoreactive cells in the DG was not changed at 2 days after single Ad-MSC injection; however, it was significantly increased by 62% 9 days after single Ad-MSC injection. At 23 days after repeated Ad-MSC application, the number of DCX-immunoreactive cells was much more increased (223% of the vehicle-treated group). At this time point, DCX protein levels were also significantly increased compared with those in the vehicle-treated group. These results suggest that the intrathecal injection of Ad-MSC could enhance endogenous cell proliferation, and the repeated Ad-MSC injection could be more efficient for an enhancement of endogenous cell proliferation and differentiation in the brain.

show abstract

Effects of Intrahepatic Bone-Derived Mesenchymal Stem Cells Autotransplantation on the Diabetic Beagle Dogs

Cited by 29 publications

References 41 publications

Increased Expression of EGR-1 in Diabetic Human Adipose Tissue-Derived Mesenchymal Stem Cells Reduces Their Wound Healing Capacity

Increased Expression of EGR-1 in Diabetic Human Adipose Tissue-Derived Mesenchymal Stem Cells Reduces Their Wound Healing Capacity

Therapeutic Doses of Multipotent Stromal Cells from Minimal Adipose Tissue

Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus After Intrathecal Treatment with Adipose-Derived Mesenchymal Stem Cells

Contact Info

Product

Resources

About