ReviewsCell-Based Therapy Using Umbilical Cord Blood for Novel Indications in Regenerative Therapy and Immune Modulation: An Updated Systematic Scoping Review of the Literature

- Cell therapy using cord blood is being used increasingly in novel applications.
- We reviewed 57 studies in a systematic search, including 25 on neurologic diseases (12 on cerebral palsy).
- Some benefit was identified in controlled studies for cerebral palsy, cirrhosis, and diabetes type 1.
- Total nucleated cells were given in most studies, with mesenchymal stromal cells in 20 studies, the majority allogeneic.
- Enrollment on registered controlled trials is encouraged.

Cell-based therapy using umbilical cord blood (UCB) is being used increasingly in novel applications. To balance heightened public expectations and ensure appropriateness of emerging cell-based treatment choices, regular evidence-based assessment of novel UCB-derived therapies is needed. We performed a systematic search of the literature and identified 57 studies (814 patients) for analysis. Sixteen of these studies (353 patients) included a control group for comparison. The most commonly reported novel indication for therapy was neurologic diseases (25 studies, 476 patients), including studies of cerebral palsy (12 studies, 276 patients). Other indications included diabetes mellitus (9 studies, 149 patients), cardiac and vascular diseases (7 studies, 24 patients), and hepatic diseases (4 studies, 106 patients). Most studies administered total nucleated cells, mononuclear cells, or CD34-selected cells (31 studies, 513 patients), whereas 20 studies described the use of UCB-derived mesenchymal stromal cells. The majority of reports (46 studies, 627 patients) described cellular products obtained from allogeneic sources, whereas 11 studies (187 patients) used autologous products. We identified 3 indications where multiple prospective controlled studies have been published: 4 of 4 studies reported clinical benefit in cerebral palsy, 1 of 3 studies reported benefit for cirrhosis, and 1 of 3 studies reported biochemical response in type 1 diabetes), although heterogeneity among the studies precluded meaningful pooled analysis of results. We anticipate a more clear understanding of the clinical benefit for specific indications once more controlled studies are reported. Patients should continue to be enrolled on registered clinical trials for novel therapies. Blood establishments, transplantation centers, and regulatory bodies need to prepare for greater clinical demand.