Abstract
Umbilical cord blood plasma (UCB-PL) contains various cytokines, growth factors, and immune modulatory factors that regulate the proliferation and function of immune cells and adult stem cells. Despite its therapeutic potential, the effects of UCB-PL treatment in conditions of ischemic brain injury have yet to be investigated. In this study, we demonstrated that both behavioral and structural impairments resulting from ischemic brain injury were significantly prevented/reversed after intravenous administration of UCB-PL relative to the vehicle control. As early as 1-week post-ischemia, an increased number of newborn cells in the subventricular zone and a reduced number of activated microglial cells in the peri-infarct area were observed in the UCB-PL group, suggesting that enhanced neurogenesis and/or the suppression of inflammation may have contributed to functional protection/recovery. Moreover, UCB-PL was more effective than plasma derived from a 65-year-old healthy adult for the treatment of ischemia-related structural and functional deficits, indicating that UCB-PL had greater therapeutic potential. This study provides valuable insights into the development of a safe, effective, and cell-free strategy for the treatment of ischemic brain damage and a much-needed alternative for patients who are ineligible for thrombolytic therapy.
Highlights
Stroke, a devastating cerebrovascular disease, is classified into ischemic and hemorrhagic subtypes based on its etiology [1, 2]
Behavioral performances were examined between the control (PBS-treated) and Umbilical cord blood plasma (UCB-PL) groups, which had received treatment every 2 days starting from the third day after Middle cerebral artery occlusion (MCAO) surgery for a total of 9 treatments (Figure 2A)
The UCB-PL group displayed significant improvements in the corner turn test compared with the control group from the first week after MCAO surgery; this functional difference became statistically significant from the second week after MCAO surgery (Figure 2C)
Summary
A devastating cerebrovascular disease, is classified into ischemic and hemorrhagic subtypes based on its etiology [1, 2]. The window of effectiveness of tissue plasminogen activator (tPA) treatment is only 4.5 h postischemic injury, which allows only 8% of stroke patients to receive tPA therapy [3, 4]. New cell-based therapeutic strategies are in development that use bone marrow- or adipose tissue-derived mesenchymal stem cells (MSCs) and neural stem cells. In the case of stem cell administration to patients, the potential risk of serious side effects such as uncontrolled growth of the transplanted cells [5] and clogging of small blood vessels by occasional unexpected cell aggregates cannot be avoided. We demonstrate that UCB-PL administration exerted therapeutic effects on both structural and behavioral recovery in a rat model of focal ischemic stroke. The results of this study provide valuable insights into the development of a safe, alternative, and cell-free therapeutic strategy for stroke patients who are ineligible for thrombolytic therapy
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