Insulin-producing cells from mesenchymal stromal cells: Protection against cognitive impairment in diabetic rats depends upon implant site
| Autor: | Nicholas Guerini Selistre, Aline Moreira, Lílian Juliana Lissner, Krista Minéia Wartchow, Letícia Rodrigues, Carlos Alberto Gonçalves, Patrícia Sesterheim, Bárbara Carolina Federhen |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Blood Glucose Glycation End Products Advanced Male medicine.medical_specialty medicine.medical_treatment Adipose tissue Hippocampal formation 030226 pharmacology & pharmacy Neuroprotection Hippocampus Rats Inbred WKY General Biochemistry Genetics and Molecular Biology Diabetes Mellitus Experimental 03 medical and health sciences 0302 clinical medicine Diabetes mellitus Internal medicine medicine Animals Insulin Cognitive Dysfunction General Pharmacology Toxicology and Pharmaceutics Pancreas business.industry Mesenchymal stem cell Mesenchymal Stem Cells General Medicine medicine.disease Rats 030104 developmental biology medicine.anatomical_structure Endocrinology Diabetes Mellitus Type 1 Adipose Tissue Hyperglycemia Implant business |
| Zdroj: | Life sciences. 251 |
| ISSN: | 1879-0631 |
| Popis: | Diabetes mellitus (DM) is a serious public health problem and can cause long-term damage to the brain, resulting in cognitive impairment in these patients. Insulin therapy for type 1 DM (DM1) can achieve overall blood glucose control, but glycemic variations can occur during injection intervals, which may contribute to some complications. Among the additional therapies available for DM1 treatment is the implantation of insulin-producing cells (IPCs) to attenuate hyperglycemia and even reverse diabetes. Here, we studied the strategy of implanting IPCs obtained from mesenchymal stromal cells (MSCs) from adipose tissue, comparing two different IPC implant sites, subcapsular renal (SR) and subcutaneous (SC), to investigate their putative protection against hippocampal damage, induced by STZ, in a rat DM1 model. Both implants improved hyperglycemia and reduced the serum content of advanced-glycated end products in diabetic rats, but serum insulin was not observed in the SC group. The SC-implanted group demonstrated ameliorated cognitive impairment (evaluated by novel object recognition) and modulation of hippocampal astroglial reactivity (evaluated by S100B and GFAP). Using GFP+ cell implants, the survival of cells at the implant sites was confirmed, as well as their migration to the pancreas and hippocampus. The presence of undifferentiated MSCs in our IPC preparation may explain the peripheral reduction in AGEs and subsequent cognitive impairment recovery, mediated by autophagic depuration and immunomodulation at the hippocampus, respectively. Together, these data reinforce the importance of MSCs for use in neuroprotective strategies, and highlight the logistic importance of the subcutaneous route for their administration. |
| Databáze: | OpenAIRE |
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