Therapeutic potential of umbilical cord mesenchymal stromal cells transplantation for cerebral palsy: a case report.
ABSTRACT Cerebral palsy is the most common motor disability in childhood. In current paper, we first report our clinical data regarding administration of umbilical cord mesenchymal stem cells (MSCs) transplantation in treatment of cerebral palsy. A 5-year-old girl with cerebral palsy was treated with multiple times of intravenous and intrathecal administration of MSCs derived from her young sister and was followed up for 28 months. The gross motor dysfunction was improved. Other benefits included enhanced immunity, increased physical strength, and adjusted speech and comprehension. Temporary low-grade fever was the only side effect during the treatment. MSCs may be a safe and effective therapy to improve symptoms in children with cerebral palsy.
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ABSTRACT: In the research, clinical, and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however, this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical, and logistical considerations, together with the propensity for native cells to form teratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs), or umbilical cord blood (UCB) stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs), and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain injury.Frontiers in Neuroscience 01/2013; 7:194.
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ABSTRACT: To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE). We enrolled infants in the intensive care nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to 4 doses adjusted for volume and red blood cell content, 1-5 × 10(7) cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post-infusion vital signs. As exploratory analyses, we compared cell recipients' hospital outcomes (mortality, oral feeds at discharge) and 1-year survival with Bayley Scales of Infant and Toddler Development, 3rd edition scores ≥85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells. Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 mL. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1-year outcomes survived with scores >85. Collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed.The Journal of pediatrics 12/2013; · 4.02 Impact Factor
Hindawi Publishing Corporation
Case Reports in Transplantation
Volume 2013, Article ID 146347, 4 pages
Therapeutic Potential of Umbilical Cord Mesenchymal Stromal
Cells Transplantation for Cerebral Palsy: A Case Report
Liming Wang,1Haijie Ji,2,3,4Jianjun Zhou,1Jiang Xie,2,3,4
Zhanqiang Zhong,1Ming Li,1Wen Bai,1Na Li,2,3,4Zijia Zhang,5Xuejun Wang,2,3,4
Delin Zhu,2,3,4Yongjun Liu,2,3,4and Mingyuan Wu2,3,4,6
1Cell Therapy Center, 323 Hospital of People’s Liberation Army, Xi’an 710054, China
2Alliancells Institute of Stem Cells and Translational Regenerative Medicine & Alliancells Bioscience Co., Ltd., Tianjin 300381, China
3Zhongyuan Union Stem Cell Bioengineering Stock Company, Tianjin 300050, China
4Beijing Alliancells-PuRui Bioscience Co., Ltd., Beijing 100052, China
5Department of Cell Biology, Oklahoma State University, Tulsa, OK 74106, USA
6Harold Hamm Oklahoma Diabetes Center and Section of Endocrinology and Diabetes in the Department of Internal Medicine,
University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Correspondence should be addressed to Yongjun Liu; firstname.lastname@example.org
and Mingyuan Wu; email@example.com
Received 24 January 2013; Accepted 13 February 2013
Academic Editors: M. Ferraresso, J. Jazbec, and M. Sadeghi
Copyright © 2013 Liming Wang et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cerebral palsy is the most common motor disability in childhood. In current paper, we first report our clinical data regarding
administration of umbilical cord mesenchymal stem cells (MSCs) transplantation in treatment of cerebral palsy. A 5-year-old girl
with cerebral palsy was treated with multiple times of intravenous and intrathecal administration of MSCs derived from her young
increased physical strength, and adjusted speech and comprehension. Temporary low-grade fever was the only side effect during
the treatment. MSCs may be a safe and effective therapy to improve symptoms in children with cerebral palsy.
Cerebral palsy is a group of severe disorders in the devel-
opment of movement and posture occurred in developing
fetal or infant brain, often accompanied with disturbances
of sensation, cognition, communication, perception, and/or
behavior and/or by a seizure . The causes of cerebral
palsy are heterogeneous with no single etiology predomi-
nating, and the main etiological factors are periventricular
intracranial hemorrhage . The prevalence in children aged
with cerebral palsy is an early-onset neuromotor impairment
. Roughly half of children with cerebral palsy also have
disabilities, epilepsy, speech and language difficulties, pri-
mary sensory impairment, and behavioral challenges .
and occupational therapy, oral medications, and orthopedic
of cerebral palsy via replacing injured or dead neuronal cells
and has proven effective in restoring injured organs and
were first identified in 1976 in the stromal compartment
of bone marrow  and are currently referred to also as
mesenchymal stromal cells . Previously, a few case reports
cells in the treatment of neurological diseases including
2Case Reports in Transplantation
spinal cord injury and basilar artery dissection [10–12].
bone marrow mononuclear cells in a cerebral palsy patient
suggested the cell transplantation is effective and safe with
encouraging functional outcome improvements .
Here we present a pediatric case to determine whether
combined intrathecal and intravenous administration of
umbilical cord MSCs is safe and effective in a patient with
2. Case Report
The study was approved by the Institutional Review Boards
of participating institutions at 323 Hospital of PLA (Xi’an,
China) and was conducted according to the principles of the
tation were obtained from the patient and her parents.
A 5-year-old girl suffering from cerebral palsy was
referred to our hospital in December 2008. The major symp-
tom was congenital growth retardation of motor function
including ambulation with tumble, disability of standing up
by her, and severe dysarthria precluding speech. Physical
examinations indicated that muscular tension of limbs was
normal, but fine motor skills were poor. Meanwhile, her
apprehension and thinking were worse than those of other
same-age children. Her functional independence measure
was 48/126. She had no epilepsia and chorea history. She
showed limited response for other treatments including
neurotrophic drugs and rehabilitation training.
MSCs were derived from umbilical cord of her younger
sister and prepared as described previously with some modi-
fications . Briefly, the whole process of MSCs preparation
was performed in a good manufacturing practice (GMP)
Regenerative Medicine located in Tianjin, China. The umbil-
trypsin for another 30min with gentle agitation at 37∘C. The
cell suspension, and then the MSCs were expanded by in
vitro culturing. The releasing criteria included cell viability
of CD73, CD90, and CD105 (>90%), and absence of CD34,
solution were administered, of which 18mL were delivered
puncture. A total of seven treatments were processed from
December 2008 to June 2009 (Table 1). During the treatment
period, the patient had one episode of temporary fever
without needing an additional treatment. No other medical
treatment except rehabilitation training was performed.
The patient was followed up for 28 months since the
last transplantation of MSCs. Symptoms before and after
MSCs treatment were carefully compared (Table 2). The
major improvement was the reduction of ambulation with
tumble. The patient was able to stand up by herself. Other
ical cord was minced into 1-2mm3fragments and incubated
with 0.075% collagenase type II for 30min and then 0.125%
CD45, CD14, CD19, and HLA DR (<2%).
(>95%), free from bacterial and viral contamination,absence
of endotoxin and immunophenotyping showing expression
For each treatment, a total of 5–10 × 106MSCs in 20mL
Table 1: Transplantation details.
Total cell count
7.5 × 106
6.2 × 106
6.3 × 106
5.7 × 106
10.2 × 106
8.5 × 106
9.1 × 106
ical strength, and adjusted speech and comprehension which
chest X-rays, routine blood test, and liver and renal function
test showed normal parameters.
Previous clinical trials showed that subarachnoid placement
of stem cells was safe without long-term side effects .
In current paper, temporary low-grade fever after adminis-
tration of umbilical cord MSCs was observed and resolved
without any treatment within 24h. At the time of writing,
no major side effects are observed during the followup for 28
The MSCs contribute to substantial neuroprotection and
neuroregeneration in the brain [16, 17]. Immature brain
may be more amenable than the mature brain to their
functionalincorporation. The patientin thispaper is less
than 10 years old, so she may benefit more from stem cell
transplantation than adult patients.
There is increasingevidence showing that administration
of MSCs may promote recovery in animal nervous disease
models including ataxic and ischemic stroke, resulting from
is reported that many MSCs lodge in the lung with systemic
delivery in an animal model and secrete anti-inflammatory
factors . The MSCs are implicated in immune regulation
resulting from suppressing initial immune responses and
clean up inflammatory factors from preexistence of immune
responses . Therefore, existence of both MSCs-specific
cytokines as early effectors and the differentiated tissue-
specific cytokines as later effectors could support brain cell
and neuronal process repair. Here we also observed that the
natural resistance to disease of the patient was strengthened;
for example, she had less frequency of influenza after MSCs
In conclusion, umbilical cord MSCs transplantation
showed the potential promise of, at least partially, improving
the gross motor dysfunction of children with cerebral palsy.
The result suggests that MSCs transplantation may be a safe
and effective way to treat cerebral palsy. Efficacy and adverse
effects in long term in a large-size cohort merit further
Case Reports in Transplantation3
Table 2: Comparison of functional independence measures before and after the last umbilical cord MSCs administration.
3rd month28th month
(4) Dressing upper
(5) Dressing lower
(7) Bladder management
(8) Bowel management
(9) Transfers: chair/wheelchair
(10) Transfers: toilet
(11) Transfers: tub/shower
(12) Locomotion: walk/wheelchair/crawl
(13) Locomotion: stairs
(16) Social interaction
(17) Problem solving
Total of FIM
L. Wang and H. Ji have contributed equally to this work.
This study was supported by the Military Medical Heath
Project to Dr. Liming Wang (no. CLZ12GA23).
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