A team from the Sant Pau Research Institute (IR Sant Pau) has discovered that basic fibroblast growth factor (bFGF) can reverse the functional impairments of adipose tissue–derived stem cells in people with type 2 diabetes. This restores their ability to proliferate, migrate, and form new blood vessels.
These cells, which under normal conditions play a key role in tissue regeneration, lose much of their effectiveness due to the adverse metabolic environment caused by diabetes. The new study indicates that bFGF can reactivate their immunomodulatory and proangiogenic behavior, restoring their proliferative potential and their ability to create new blood vessels, which are diminished by the disease.
The research, published in the journal Diabetologia, demonstrates that bFGF treatment not only enhances the functional potential of these cells but also modifies their microRNA (miRNA) profile—small molecules that regulate gene expression and are directly involved in blood vessel formation and vascular repair. These findings open the door to new personalized regenerative medicine strategies for vascular complications associated with type 2 diabetes.
Type 2 diabetes is a metabolic disease that, in addition to altering blood glucose levels, damages the vascular system and compromises the body’s ability to repair tissues. This dysfunction affects the heart, kidneys, brain, and lower limbs, creating a high risk of cardiovascular complications.
Adipose tissue–derived stem cells are an abundant and easily accessible source of cells with therapeutic potential. They can promote the formation of new blood vessels and support tissue regeneration, but in people with diabetes, they lose part of these properties: their proliferation decreases, they migrate less, and their transcriptomic profile is altered.
“We already knew that the metabolic environment of diabetes deeply impacts the behavior of stem cells,” explains Dr. Gemma Arderiu, principal investigator of the study and head of the Cell Therapy and Angiogenesis in Ischemic Pathology Group at IR Sant Pau. “That’s why we wondered whether it might be possible to ‘re-educate’ them before using them for therapeutic purposes. What we observed is very promising: bFGF treatment restores cellular functions that were severely impaired.”
The research team obtained samples of subcutaneous and visceral adipose tissue from each of the eight patients who participated in the study—four with type 2 diabetes and morbid obesity and four non-diabetic individuals of normal weight. From these samples, the researchers isolated the stem cells and cultured them for nine days in the presence of bFGF, a protein widely studied for its role in cell growth, wound healing, and blood vessel formation.
The treatment proved highly effective. The cells derived from patients with diabetes, which initially showed very limited proliferation and reduced migratory capacity, recovered their ability to proliferate and migrate, behaving similarly to cells from non-diabetic individuals. This effect was particularly notable in cells from visceral adipose tissue, which are most affected by the inflammation and metabolic stress characteristic of the disease.
To assess whether this recovery translated into functional improvement, the team performed various in vitro and in vivo assays. In three-dimensional cultures and in mouse models, the bFGF-treated cells showed a greater ability to organize into capillary-like structures and generate new blood vessels, confirming that the treatment restores their angiogenic and reparative potential.
“We have observed that bFGF functionally restores the angiogenic properties of endothelial cells,” explains Dr. Arderiu. “It reactivates their proangiogenic potential and their capacity to interact with other vascular cells and form new vascular structures. It’s a remarkable recovery, considering the extent of damage that diabetes causes in these cells.”
The study also reveals how bFGF achieves this reparative effect. The researchers analyzed the miRNA profile—small molecules that act as genetic “switches,” regulating the activity of numerous genes involved in key processes such as cell proliferation, blood vessel formation, and cellular aging.
In people with diabetes, these miRNAs are often dysregulated: some are overexpressed, suppressing cell growth, while others fail to activate when needed. This imbalance prevents stem cells from functioning properly and limits their ability to repair damaged tissues.
Treatment with bFGF restored part of this lost balance. After exposure to the factor, the researchers observed a reduction in miR-24, miR-145, and miR-140—linked to growth inhibition and cellular senescence—and an increase in miR-17, a positive regulator of proliferation and survival. This shift in the miRNA pattern reactivated key molecular pathways, including TGF-β, Wnt, and integrin signaling, which are fundamental for blood vessel formation and repair.
“We could say that bFGF not only acts on the surface of the cell but also enters its internal programming and corrects it,” explains Dr. Arderiu. “This molecular adjustment allows the cells to once again respond to growth and regeneration signals, as they would in a healthy environment.”
The researcher adds that this cellular plasticity opens a very encouraging horizon. “If we can modulate gene expression in cells using biological molecules like bFGF, we can design more effective, patient-tailored regenerative therapies. It’s an important step toward precision medicine in metabolic and vascular diseases.”
The study’s results point to a paradigm shift in the use of stem cells as a therapeutic tool. Treatment with bFGF not only restores their angiogenic potential but also enhances their adaptability and regenerative response, opening new possibilities for application in patients with type 2 diabetes.
“The ability to recover the therapeutic potential of a patient’s own cells is a highly significant breakthrough,” says Dr. Gemma Arderiu. “This study demonstrates that cells affected by diabetes are not lost; with the right strategy, they can regain their reparative function and help regenerate damaged tissues.”
She further emphasizes that this approach “represents a step forward toward more personalized and safer medicine, based on the use of the patient’s own cells pretreated in the laboratory.” According to her, bFGF preconditioning could be incorporated as a preparatory step in regenerative therapies aimed at restoring vascular function or improving wound healing in different types of lesions.
The authors acknowledge that the study was conducted with a limited number of human samples due to the difficulty of obtaining both visceral and subcutaneous tissue from the same patient. Even so, the results provide a solid foundation for future preclinical research aimed at validating the safety and efficacy of the treatment in models of diabetic vascular disease.
“These results strengthen our commitment to translational research that brings laboratory advances closer to clinical practice,” concludes Dr. Arderiu. “We show that even under adverse conditions like type 2 diabetes, stem cells retain regenerative potential that can be reactivated. We just need to find the right stimulus to awaken it.”
The study was carried out at the Sant Pau Research Institute (IR Sant Pau) in collaboration with the Cell Therapy Network (TERAV and TERAV+), the Biomedical Research Networking Center in Cardiovascular Diseases (CIBERCV), and the University of Barcelona (UB). The research was funded by the Carlos III Health Institute and the Government of Catalonia.
Article reference:
Civit-Urgell A, Peña E, Bejar MT, Moscatiello F, Vilahur G, Badimon L, Arderiu G. bFGF rescues dysfunctional properties of adipose-derived stem cells from individuals with type 2 diabetes by modulating their miRNA profile. Diabetologia 2025. https://doi.org/10.1007/s00125-025-06533-0
