Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

Abstract

Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders.

Therapeutic Potential of Mesenchymal Stem Cells vs. Estradiol Benzoate or Avosoya on the Cerebellar Cortex of Ovariectomized Adult Albino Rats

“…MSCs were found to prevent the overexpression of GFAP in cerebellum. This reduced GFAP protein levels and immune reactivity in the cerebellum suggests that grafted cells could be involved in the modulation of astrogliosis [31].…”

“…So, they can be the future form of treatment to bypass the blood brain barrier. Calatrava-Ferreras et al [31] reported HUCBMCs reached the cerebellum and brain stem of rats. They added that, grafted cells reduced neuronal loss, prevented cerebellar glial reactivity and hence, improved motor coordination in ataxic rats.…”

“…Cells were counted under microscope by using haemocytometer and calculated. MSCs (4.5 × 10 6 cells in 250 μL PBS), were injected into the tail vein of HUCB-MSCs treated group [31].…”

An experimental study of menopause induced by bilateral ovariectomy and mechanistic effects of mesenchymal stromal cell therapy on the parotid gland of a rat model

“…The rats were divided equally into three groups (n=6): sham-operated (SHAM), ovariectomized (OVX), and OVX + hUCB-MSCs. The OVX + hUCB-MSCs group received an injection of 4.5 x 10 6 hUCB-MSCs dissolved in 250 μL PBS on the tail vein two months after ovariectomy for four consecutive weeks (twice in a week) (Calatrava-Ferreras et al, 2012). However, both SHAM and OVX groups were injected with vehicle (PBS) only.…”

Improvements in a Case of Sensory Ataxia Through Cell Transplantation

“…Intravenous administration of mesenchymal stem cells in ataxic mice has shown that they can rescue the degenerating cells with the help of neurotropic factors such as NGF, BDNF and NT-3 by integrating into the central nervous system [25]. Another study in the rat model demonstrated that intravenous administration of human umbilical cord blood stem cells (HuUCBMCs) reduced neuronal loss and upregulated the expression of proteins critical for cell survival [26]. Clinical studies with BMMNCs showed efficacy in delaying the progression of cerebellar ataxia supported by improvements in various outcome measures such as the Berg Balance Scale (BBS), activity of daily living scale (ADL) and International The objective of our study was to evaluate the safety, feasibility, and efficacy of autologous BMMNCs in the treatment of patient with sensory ataxia.…”