Angiogenic properties of human placenta-derived adherent cells and efficacy in hindlimb ischemia

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• 作者：Aleksandar Francki ; PhD ; ^{afrancki@celgene.com" class="auth_mail" title="E-mail the corresponding author} ; Kristen Labazzo ; PhD ; Shuyang He ; PhD ; Ellen Z. Baum ; PhD ; Stewart E. Abbot ; PhD ; Uri Herzberg ; DVM ; PhD ; MBA ; Wolfgang Hofgartner ; MD ; DSc ; Robert Hariri ; MD ; PhD ; on behalf of the Celgene Cellular Therapeutics Research GroupAleksandr Kaplunovsky ; Jennifer Paredes ; Allan Reduta ; Eric Law ; Ewa Fik ; Sascha Abramson ; Vivian R. Albert ; Itschak Lamensdorf
• 刊名：Journal of Vascular Surgery
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：64
• 期：3
• 页码：746-756.e1
• 全文大小：2398 K

文摘

Human placenta-derived adherent cells (PDACs) are a culture-expanded, undifferentiated mesenchymal-like population from full-term placental tissue and were previously shown to possess anti-inflammatory and immunomodulatory properties. PDACs (formulated as PDA-002) are in clinical trials for peripheral arterial disease with diabetic foot ulcer. In the current study, we examined their angiogenic and tissue reparative properties.

Methods

The effects of PDACs on survival and tube formation of human umbilical vein endothelial cells (HUVECs) were tested using conditioned media and noncontact coculture. Angiogenic effects were assessed in the chick chorioallantoic membrane assay. Hindlimb ischemia (HLI) was induced in mice and rats by femoral artery transection, and blood flow and blood vessel density were monitored in vivo by laser Doppler and angiography in the ischemic and control limbs. Tissue damage and regeneration in HLI were examined in histologic sections of quadriceps muscle stained with hematoxylin and eosin, and newly synthesized blood vessels were detected by indoxyl-tetrazolium staining for alkaline phosphatase.

Results

PDACs enhanced the survival of serum-starved HUVECs and stimulated HUVEC tube formation, and in the chick chorioallantoic membrane assay, PDACs stimulated blood vessel formation. In HLI, intramuscular administration of PDACs resulted in improved blood flow and vascular density, and in quadriceps muscle, tissue regeneration and increased numbers of blood vessels were observed.

Conclusions

PDACs exhibited various activities consistent with angiogenesis and tissue repair, supporting the continued investigation of this cell therapy as treatment for vascular disease-related indications.