Publication:
PDGF Restores the Defective Phenotype of Adipose-Derived Mesenchymal Stromal Cells from Diabetic Patients.

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2018-08-16

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Capilla-González, Vivian
López-Beas, Javier
Escacena, Natalia
Aguilera, Yolanda
de la Cuesta, Antonio
Ruiz-Salmerón, Rafael
Martín, Franz
Hmadcha, Abdelkrim
Soria, Bernat

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Abstract

Diabetes is a chronic metabolic disorder that affects 415 million people worldwide. This pathology is often associated with long-term complications, such as critical limb ischemia (CLI), which increases the risk of limb loss and mortality. Mesenchymal stromal cells (MSCs) represent a promising option for the treatment of diabetes complications. Although MSCs are widely used in autologous cell-based therapy, their effects may be influenced by the constant crosstalk between the graft and the host, which could affect the MSC fate potential. In this context, we previously reported that MSCs derived from diabetic patients with CLI have a defective phenotype that manifests as reduced fibrinolytic activity, thereby enhancing the thrombotic risk and compromising patient safety. Here, we found that MSCs derived from diabetic patients with CLI not only exhibit a prothrombotic profile but also have altered multi-differentiation potential, reduced proliferation, and inhibited migration and homing to sites of inflammation. We further demonstrated that this aberrant cell phenotype is reversed by the platelet-derived growth factor (PDGF) BB, indicating that PDGF signaling is a key regulator of MSC functionality. These findings provide an attractive approach to improve the therapeutic efficacy of MSCs in autologous therapy for diabetic patients.

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MeSH Terms

Animals
Cell Differentiation
Cell Proliferation
Cell- and Tissue-Based Therapy
Cells, Cultured
Diabetes Complications
Diabetes Mellitus
Humans
Inflammation
Mesenchymal Stem Cells
Mice
Mice, SCID
Osteogenesis
Phenotype
Proto-Oncogene Proteins c-sis
Signal Transduction
Wound Healing

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Keywords

PDGF, adipose-derived mesenchymal stromal cells, critical limb ischemia, diabetes, homing, migration, proliferation, thrombotic state

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