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ArticleStem cell reviews and reports2026

Type 2 Diabetes-Induced Molecular and Functional Impairment of Adipose Tissue-Derived Mesenchymal Stromal Cells (ASCs) and Interferon Gamma Priming for Enhanced Diabetic ASC-Based Therapy.

Alaa Zeinhom, Ammar Y Mohamed, Nahla N Abdel-Aziz, Mostafa Sayed Diab, Amir M H Salem, Noha N Yassen, Eman E A Mohammed, Amal M Mohamed, Ola M Eid, Shymaa H Hussein and 8 more

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Article in Stem cell reviews and reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

18 authors.

Alaa ZeinhomDepartment of Biotechnology, Faculty of Science, Cairo University, Cairo, 12316, Egypt.
Ammar Y MohamedDepartment of Biotechnology, Faculty of Agriculture, Cairo University, Cairo, 12316, Egypt.
Nahla N Abdel-AzizDepartment of Human Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre (NRC), Cairo, 12622, Egypt.
Mostafa Sayed DiabDepartment of General and Laparoscopic Surgery, 6th of October Hospital for Health Insurance, Cairo, 12611, Egypt.
Amir M H SalemDepartment of Pathology, Medical Research and Clinical Studies Institute, NRC, Cairo, 12622, Egypt.
Noha N YassenDepartment of Pathology, Medical Research and Clinical Studies Institute, NRC, Cairo, 12622, Egypt.
Eman E A MohammedDepartment of Human Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre (NRC), Cairo, 12622, Egypt.
Amal M MohamedDepartment of Human Cytogenetic, Human Genetics and Genome Research Institute, NRC, Cairo, 12622, Egypt.
Ola M EidDepartment of Human Cytogenetic, Human Genetics and Genome Research Institute, NRC, Cairo, 12622, Egypt.
Shymaa H HusseinDepartment of Human Cytogenetic, Human Genetics and Genome Research Institute, NRC, Cairo, 12622, Egypt.
Marwa FaridDepartment of Human Cytogenetic, Human Genetics and Genome Research Institute, NRC, Cairo, 12622, Egypt.
Engy K TharwatBioinformatics Group, Center for Informatics Science, School of Information Technology and Computer Science, Nile University, Giza, Egypt.
Kholoud A AliDepartment of Animal Behaviour and Management, Faculty of Veterinary Medicine, Cairo University, Cairo, 12316, Egypt.
Hesham A ElmeligyDepartment of General Surgery, Theodor Billharz Research Institute, Giza, 12411, Egypt.
Sahar A FadallahDepartment of Biotechnology, Faculty of Science, Cairo University, Cairo, 12316, Egypt.
Osama AzmyStem Cell Research Unit, Medical Research Centre of Excellence, NRC, Cairo, 12622, Egypt.
Nourhan Abu-ShahbaDepartment of Human Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre (NRC), Cairo, 12622, Egypt.
Marwa MahmoudDepartment of Human Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre (NRC), Cairo, 12622, Egypt. marwa_aromatic_85@yahoo.com.

Funding

Science and Technology Development Fund 26221
6 · The paper itself

Abstract

backgroundTransplantation of adipose-derived mesenchymal stromal cells (ASCs) or their insulin-producing derivatives holds promise for diabetes mellitus therapy due to their regenerative properties. However, the harsh microenvironment in type 2 diabetes (T2D) likely impairs autologous ASC efficacy.

aimThis study investigated transcriptomic alterations and therapeutic efficacy of ASCs from T2D patients (dASCs) in experimental diabetes, compared to healthy donors (ndASCs), and evaluated whether inflammatory priming could enhance dASC functionality.

methodsdASCs and ndASCs were characterized phenotypically and functionally. Differentially expressed genes (DEGs) were identified via microarray profiling of basal and IFN-γ/TNF-α-primed cells. miRNA-transcription factor (TF) coregulatory networks were constructed for key DEGs. In vivo, anti-hyperglycemic effects, islet regeneration, insulin expression, and local inflammation modulation were assessed in streptozotocin (STZ)-induced diabetic rats by transplanting dASCs, ndASCs, or IFN-γ-primed dASCs (p.dASCs).

resultsDEGs in dASCs were significantly enriched in inflammation, glycerolipid metabolism, cell adhesion, cytoskeleton remodeling, angiogenesis, and insulin or hypoxia-related responses. EGFR/ERBB2 signaling, with downstream Ras/MAPK and PI3K/AKT cascades, and endocrine resistance-related pathways were significantly overrepresented. Although inflammatory responses were broadly shared, cytokine priming further exacerbated endocrine resistance and oxidative phosphorylation defects-associated transcriptomic signatures in dASCs. Key DEGs (EGFR, ERBB2, ESR1, FOS, IL1B, JUN, KRAS, MMP9, RUNX2) were identified as contributors to insulin resistance-related pathways and were used to construct a miRNA-TF coregulatory circuit for mechanistic and therapeutic hypothesis-generation. In the STZ-diabetes model, dASCs displayed limited regenerative capacity and attenuated immunomodulatory function; however, these potentials were partially restored by p.dASCs. Favorable trends in glycemic control parameters were observed with ndASCs, and C-peptide levels were significantly higher in p.dASC-treated rats compared with those receiving non-primed dASCs.

conclusionThe study suggests a multifaceted dysregulated transcriptomic signature in dASCs, prominently including endocrine resistance-related pathways. The therapeutic efficacy of dASCs is partially rescued by IFN-γ priming, which supports the potential of tailored preconditioning strategies for improving autologous cell therapy in diabetes.

Indexed as

Adipose TissueDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Interferon-gammaMesenchymal Stem CellsMesenchymal Stem Cell TransplantationAnimalsHumansMaleRatsTranscriptomeInterferon-gammaAdipose-derived mesenchymal stromal cellsEndocrine resistanceIFN-γ primingIslet regenerationTranscriptomeType 2 diabetes

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.