The angiogenesis promoter, proadrenomedullin N-terminal 20 peptide (PAMP), improves healing in both normoxic and ischemic wounds either alone or in combination with autologous stem/progenitor cells
Natalio García-Honduvilla1, Alberto Cifuentes1, Juan Manuel Bellón2, Julia Buján1 and Alfredo Martínez3
1Department of Medical Specialities, 2Department of Surgery, School of Medicine, University of Alcalá, Alcalá de Henares, Madrid and 3Angiogenesis Study Group, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.
Offprint requests to: Alfredo Martínez, Angiogenesis Study Group, Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logroño, Spain. e-mail: amartinezr@riojasalud.es
Summary. A combination of vascular pathologies and other complicating factors results in chronic wounds which constitute a serious burden for both patients and national health systems, due to prolonged hospital stays, high costs, and prolonged nursing staff dedication. Here we investigate whether proadrenomedullin N-terminal 20 peptide (PAMP), a naturally occurring peptide of the skin with antimicrobial and proangiogenic properties, either alone or in combination with autologous skeletal muscle stem/progenitor cells, acts as a wound healing factor. The rabbit ear was chosen as a test system, since it offers a reliable model for normoxic and ischemic wounds. Topical treatments with PAMP, stem/progenitor cells, or a combination of both, resulted in significant improvements of healing, when compared to untreated wounds. PAMP was very effective in promoting reepithelialization and angiogenesis, whereas treatment with stem/progenitor cells alone resulted in less wound contraction. Interestingly, the combination of PAMP and stem/progenitor cells, while maintaining angiogenic potency, reverted to the contraction levels observed in the untreated controls. Under ischemic conditions, generalized necrosis of the dermis and the underlying cartilage was observed in untreated wounds. Treatments of these wounds with PAMP or stem/progenitor cells allowed a timely recovery. In conclusion, PAMP either alone or in combination with autologous stem/progenitor cells may provide a useful tool for improving wound healing both in normoxic and ischemic conditions. Histol Histopathol 28, 115-125 (2013)
Key words: PAMP, Wound healing, Rabbit ear model, Ischemic wounds, Stem/progenitor cells
DOI: 10.14670/HH-28.115