Transient silencing of TGF‐β1 reverses myelopoietic bias in older diabetic CD34+ cells

Adult circulating CD34+ stem progenitor cells (HSPCs) participate in vascular repair by stimulating angiogenic functions of the endothelium via paracrine mechanisms. Aging and diabetes are associated with reduced number and impaired vasculogenic potential of CD34+cells. Previous studies showed that...

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Published in:The FASEB journal 2022-05, Vol.36 (S1), p.n/a
Main Authors: Jahan, Jesmin, Montes de Oca, Ildamaris, Meissner, Brian, Maghrabi, Ahmad, Quiroz‐Olvera, Julio, Lopez‐Yang, Christine, Garcia, Charles, Jarajapu, Yagna Prasada Rao
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Language:English
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Summary:Adult circulating CD34+ stem progenitor cells (HSPCs) participate in vascular repair by stimulating angiogenic functions of the endothelium via paracrine mechanisms. Aging and diabetes are associated with reduced number and impaired vasculogenic potential of CD34+cells. Previous studies showed that diabetic dysfunction was largely due to the paracrine pro‐inflammatory and anti‐angiogenic switch in the phenotype of CD34+ cells. Furthermore, diabetic cells have a higher potential to generate pro‐inflammatory monocyte‐macrophages. We have recently shown that older‐diabetic (DB) cells have increased expression of transforming growth factor β1 (TGF‐β1) compared to the age‐matched nondiabetic (ND) cells. Transient silencing of this pleiotropic regulator restored reparative functions such as migration, proliferation, and nitric oxide generation. The current study tested the hypothesis that TGF‐β1‐silencing reverses myelopoietic bias and paracrine pro‐inflammatory phenotype in CD34+ cells derived from diabetic older adults. Expression of alarmins and receptor for advanced glycation end‐products (RAGE) were evaluated. CD34+ cells were isolated from either male or female non‐diabetic (ND) (n=31) or diabetic (DB), both type 1 and type 2, (n=39) subjects. Phosphorodiamidate morpholino oligomers (PMO) were used for TGF‐β1‐silencing. Circulating CD34+cells and monocyte‐macrophages were enumerated by flow cytometry in both groups. Gene‐expression assays were carried out by qPCR. Myelopoiesis was determined by CFU‐GM assay followed by characterization of monocytes and macrophages by flow cytometry. Circulating CD34+ cells (p
ISSN:0892-6638
1530-6860
DOI:10.1096/fasebj.2022.36.S1.R2811