Investigating the potential of the secretome of mesenchymal stem cells derived from sickle cell disease patients

Autoři: Tiago O. Ribeiro aff001;  Brysa M. Silveira aff001;  Mercia C. Meira aff001;  Ana C. O. Carreira aff002;  Mari Cleide Sogayar aff002;  Roberto Meyer aff001;  Vitor Fortuna aff001
Působiště autorů: Health Science Institute, Federal University of Bahia, Salvador, BA, Brazil aff001;  Cell and Molecular Therapy Center NUCEL-NETCEM, School of Medicine, Internal Medicine Department, University of São Paulo, São Paulo, SP, Brazil aff002;  Chemistry Institute, Biochemistry Department, University of São Paulo, São Paulo, SP, Brazil aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222093


Sickle cell disease (SCD) is a monogenic red cell disorder associated with multiple vascular complications, microvessel injury and wound-healing deficiency. Although stem cell transplantation with bone marrow-derived mesenchymal stem cells (BMSC) can promote wound healing and tissue repair in SCD patients, therapeutic efficacy is largely dependent on the paracrine activity of the implanted BM stromal cells. Since in vitro expansion and culture conditions are known to modulate the innate characteristics of BMSCs, the present study investigated the effects of normoxic and hypoxic cell-culture preconditioning on the BMSC secretome, in addition to the expression of paracrine molecules that induce angiogenesis and skin regeneration. BMSCs derived from SCD patients were submitted to culturing under normoxic (norCM) and hypoxic (hypoCM) conditions. We found that hypoxically conditioned cells presented increased expression and secretion of several well-characterized trophic growth factors (VEGF, IL8, MCP-1, ANG) directly linked to angiogenesis and tissue repair. The hypoCM secretome presented stronger angiogenic potential than norCM, both in vitro and in vivo, as evidenced by HUVEC proliferation, survival, migration, sprouting formation and in vivo angiogenesis. After local application in a murine wound-healing model, HypoCM showed significantly improved wound closure, as well as enhanced neovascularization in comparison to untreated controls. In sum, the secretome of hypoxia-preconditioned BMSC has increased expression of trophic factors involved in angiogenesis and skin regeneration. Considering that these preconditioned media are easily obtainable, this strategy represents an alternative to stem cell transplantation and could form the basis of novel therapies for vascular regeneration and wound healing in individuals with sickle cell disease.

Klíčová slova:

Angiogenesis – Endothelial cells – Hypoxia – Medical hypoxia – Tissue repair – Wound healing – Neurobiology of disease and regeneration – Sickle cell disease


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2019 Číslo 10