Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study

Abstract

Stroke is a major cause of death and long‐term disability, affecting one in six people worldwide. The only currently available approved pharmacological treatment for ischemic stroke is tissue plasminogen activator; however, relatively few patients are eligible for this therapy. We hypothesized that intravenous (IV) infusion of banked unrelated allogeneic umbilical cord blood (UCB) would improve functional outcomes in patients with ischemic stroke. To investigate this, we conducted a phase I open‐label trial to assess the safety and feasibility of a single IV infusion of non‐human leukocyte antigen (HLA) matched, ABO matched, unrelated allogeneic UCB into adult stroke patients. Ten participants with acute middle cerebral artery ischemic stroke were enrolled. UCB units were matched for blood group antigens and race but not HLA, and infused 3–9 days post‐stroke. The adverse event (AE) profile over a 12 month postinfusion period indicated that the treatment was well‐tolerated in these stroke patients, with no serious AEs directly related to the study product. Study participants were also assessed using neurological and functional evaluations, including the modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS). At 3 months post‐treatment, all participants had improved by at least one grade in mRS (mean 2.8 ± 0.9) and by at least 4 points in NIHSS (mean 5.9 ± 1.4), relative to baseline. Together, these data suggest that a single i.v. dose of allogeneic non‐HLA matched human UCB cells is safe in adults with ischemic stroke, and support the conduct of a randomized, placebo‐controlled phase 2 study. stem cells translational medicine 2018;7:521–529

Neurovascular effects of umbilical cord blood-derived stem cells in growth-restricted newborn lambs

“…In turn, altered cell interactions lead to an increased risk of BBB breakdown and may have significant adverse implications for injury-induced angiogenesis and repair [19]. Administration of UCBC in adult stroke induces changes in the neurovasculature, resulting in reduced brain neuropathology and improved neurological outcome [20,21]. It is unknown whether UCBC therapy mediates similar effects on the neurovascular unit in the neonatal brain.…”

Stem Cells Translational Medicine

“…When compared with bone marrow‐derived cells, UCB cells display improved immunotolerance and availability for infusion and may bolster recovery by downregulating inflammation and promoting neuroprotection and plasticity. Encouragingly, Laskowitz et al report that patients tolerated UCB therapy, did not suffer from any serious adverse events noted, and all participants exhibited improvements in functional outcome by 3 months postinfusion . The authors hope that these results, reported in STEM CELLS Translational Medicine , will support a randomized, placebo‐controlled phase II study.…”

Rapid review: next generation of cord blood banks; transplantation and beyond

“…Discussion with local medicine agencies is required. There are many attempts to produce medicinal products derived from cryopreserved CB, including: allogeneic NK cells; T regs for tolerance treatments; antigen‐specific T cell lines; CB‐derived universal CAR‐T cells; off‐the‐shelf, expanded, CB‐derived CD34+ cells; and MNCs to treat condition like autism, cerebral palsy, or stroke . In our institution, we have started two approaches for developing cell banks: first, development of Good Manufacturing Practice (GMP)‐grade induced pluripotent stem cells (IPSCs) from confirmed homozygous donations.…”