Autologous Cord Blood Therapy for Infantile Cerebral Palsy: From Bench to Bedside

Abstract

About 17 million people worldwide live with cerebral palsy, the most common disability in childhood, with hypoxic-ischemic encephalopathy, preterm birth, and low birth weight being the most important risk factors. This review will focus on recent developments in cell therapy for infantile cerebral palsy by transplantation of autologous umbilical cord blood. There are only 4 publications available at present; however, the observations made along with experimental data in vivo and in vitro may be of utmost importance clinically, so that a review at an early developmental stage of this new therapeutic concept seems justified. Particularly, since the first published double-blind randomized placebo-controlled trial in a paradigm using allogeneic cord blood and erythropoietin to treat cerebral palsy under immunosuppression showed beneficial therapeutic effects in infantile cerebral palsy, long-held doubts about the efficacy of this new cell therapy are dispelled and a revision of therapeutic views upon an ailment, for which there is no cure at present, is warranted. Hence, this review will summarize the available information on autologous cord blood therapy for cerebral palsy and that on the relevant experimental work as far as potential mechanisms and modes of action are concerned.

Therapeutic potential of human embryonic stem cell transplantation in patients with cerebral palsy

“…Studies related to the use of hESC therapy in patients with CP are few however; the use of cord stem cells in CP patients has been evaluated for efficacy in studies from the past. Transplantation of cord stem cells in a 2.5 year old boy with CP demonstrated significant improvement in motor function at week 4 of therapy, normal EEG and partial recovery from vision loss at week 7 of therapy [ 19 ]. Another study examining the efficacy of stem cells in a 6 year old CP patient showed significant improvement in motor function within 6 months of therapy and also showed cognitive, speech, and sensory improvements [ 20 ].…”

First Autologous Cord Blood Therapy for Pediatric Ischemic Stroke and Cerebral Palsy Caused by Cephalic Molding during Birth: Individual Treatment with Mononuclear Cells

“…We report a rare case of traumatic neonatal ischemic stroke with hemiplegic cerebral palsy caused by functional cephalopelvic disproportion and parietal head depression due to a “long pelvis” of the mother [ 2 ] that was treated with autologous cord blood mononuclear cells [ 6 ]. The ischemic stroke resulted from a traumatic occlusion of a penetrating thalamostriatal tributary of the left middle cerebral artery supplying the white matter beyond the basal ganglia, a unique feature of the developing brain [ 7 ].…”

“…Thus, neurotrophic (e.g., BDNF, VEGF), synaptotrophic (e.g., NGF), anti-inflammatory (e.g., Il-6, Il-8, and Il-10), antigliotic (e.g., Cx43), antiapoptotic, and proangiogenic neuroregenerative effects are entrained resulting in significant functional neuroregeneration [ 12 – 16 ]. The beneficial effects of cord blood mononuclear cells observed after acute brain damage caused by hypoxic-ischemia include reduced spastic paresis and recovery of gross motor function, fine motor coordination, muscle strength, somatosensory cortical processing, and, as observed in children, recovery of cognition, vision, and active and receptive speech competence [ 4 , 6 , 9 , 11 , 13 ]. To what extent these processes may be involved in neuroregeneration after late transplantation of autologous cord blood mononuclear cells as in the present case remains to be established in further systematic clinical research.…”

“…Of note is the delayed transplantation of the mononuclear cells approximately 5 years after the insult, and it may be argued that in this case the balance of evidence suggests rather a spontaneous recovery from stroke than a therapeutic effect of cell treatment. Of course, this view cannot be rebutted in an individual treatment and most of the experimental evidence votes for early intervention; however, there already exists clinical evidence for successful treatment of cerebral palsy using autologous [ 6 , 17 ] and allogeneic [ 18 ] cord blood several years after the insult. The mechanisms involved in therapeutic effects after delayed mononuclear cell treatment still await elucidation.…”

A New Approach to Cerebral Palsy Treatment: Discussion of the Effective Components of Umbilical Cord Blood and its Mechanisms of Action

“…The UCB components involved in cell therapy research are shown in Table 1. Compared with other types of stem cells, those from the UCB have advantages in terms of CP treatment safety and efficacy 22,25,34 , ethics 35 , non-neoplastic proliferation, accessibility, ease of preservation 36 , and regulation of immune responses 25 , based on findings in animal models and clinical trials 28,[37][38][39][40] . In animal studies, UCB cell therapy has made substantial progress (migration to sites 41 , improvement of functional loss 42 , and prevention of white matter damage 43 ).…”