Safety and efficacy of intramuscular human placenta‐derived mesenchymal stromal‐like cells (cenplacel [PDA‐002]) in patients who have a diabetic foot ulcer with peripheral arterial disease

Abstract

The objective of this study was to examine the safety of cenplacel (PDA‐002) in patients with peripheral arterial disease (PAD) and a diabetic foot ulcer (DFU). Cenplacel is a mesenchymal‐like cell population derived from full‐term human placenta. This phase 1, dose‐escalation study investigated cenplacel in diabetic patients with chronic DFUs (Wagner grade 1 or grade 2) and PAD [ankle‐brachial index (ABI) >0·5 and ≤0·9], enrolled sequentially into each of four dose cohorts (3 × 106, 10 × 106, 30 × 106 and 100 × 106 cells; administered intramuscularly on study days 1 and 8 in combination with standard of care). Overall, cenplacel was well tolerated in all 15 patients in the study. Before enrollment, nine patients had an ulcer for ≥6 months and 11 had an ABI of 0·7–0·85. No patient met dose‐limiting toxicity criteria and no treatment‐related serious adverse events were reported. There was preliminary evidence of ulcer healing in seven patients (five complete; two partial) within 3 months of cenplacel treatment, and circulating endothelial cell levels (a biomarker of vascular injury in PAD) were decreased within 1 month. Cenplacel was generally safe and well tolerated in patients with chronic DFUs and PAD. Outcomes from this study informed the doses, endpoints, biomarkers and patient population for an ongoing phase 2 trial.

Sugar-Lowering Drugs for Type 2 Diabetes Mellitus and Metabolic Syndrome—Strategies for In Vivo Administration: Part-II

“…Some considerations to keep in mind are: avoidance of irritating compounds or accidental nerve injection, which may lead to paresis, paralysis, localized muscle fiber destruction, and even necrosis [83,84]. New therapies are recently being explored using this route, such as the intramuscular administration of human placenta-derived mesenchymal stromal-like cells for patients who have a diabetic foot ulcer with peripheral arterial disease [85].…”

The preclinical and clinical implications of fetal adnexa derived mesenchymal stromal cells in wound healing therapy

“…Quin et al 169 derived from the full-term human placenta) has been reported so far using FAD-MSCs. 171 A summary of clinical trials that investigates the healing potential of FAD-MSCs, registered on the website of the clinical trials data bank at the National Institutes of Health (www.clinicaltrials.gov) is listed in Table 4.…”

Therapeutic strategies for skin regeneration based on biomedical substitutes

“…Among the different cells applied by injectable cell solutions are included MSCs (NCT02669199, NCT01750749), human autologous adipose‐derived stromal vascular fraction (NCT01813279), bone marrow‐derived cells (NCT01750749), human placenta‐derived cells (NCT01859117), melanocytes and keratinocytes (NCT02510651), and even human umbilical cord blood derived‐universal stem cells (NCT01927705). With the use of intramuscular human placenta‐derived mesenchymal stromal‐like cells in patients with peripheral arterial disease (PAD) and a diabetic foot ulcer (DFU), preliminary evidence of ulcer healing was shown in seven out of 15 patients, and circulating endothelial cell levels (as a vascular trauma in peripheral artery disease biomarker) were decreased within 1 month (NCT01859117) …”

“…With the use of intramuscular human placenta-derived mesenchymal stromal-like cells in patients with peripheral arterial disease (PAD) and a diabetic foot ulcer (DFU), preliminary evidence of ulcer healing was shown in seven out of 15 patients, and circulating endothelial cell levels (as a vascular trauma in peripheral artery disease biomarker) were decreased within 1 month (NCT01859117). 82 Regarding human umbilical cord blood derived-universal stem cells (hUCB-MSCs), clinical application in the treatment of atopic dermatitis (AD) demonstrated for the first time, marked an improvement of AD features with cell therapeutics without noteworthy adverse events. 83 Nevertheless, other cell-based products such as the use PRP (NCT02832583), platelet- Therapeutic strategies for skin healing rich-fibrin (NCT01957124) and amnion-derived cellular cytokine (NCT02389777, NCT01715012) are being addressed.…”