Feasibility of Cell Therapy in Multiple Sclerosis: A Systematic Review of 83 Studies.
Author: Ardeshiry Lajimi A, Hagh MF, Saki N, Mortaz E, Soleimani M, Rahim F.
28,272 Initial Participants. 2,364 Potential Selections. 652 Eligibility. 83 Selected.
Article #1: Neural Stem Cells (NSCs) for the Treatment of MS
Purpose of the study: Experimental and clinical use of stem cells and the possible
mechanisms in the treatment of MS.
Methods: (Tissue Therapy and MS conditions were the identifiers)
8 Neural Stem Cells - Glial cells in humans and 46C-NS cells in mice.
Results: The results may pave the road for the utilization of stem cells for the treatment of
MS. However a lot of work still needs to be done to prove their clinical effectiveness and
safety.
Hypothesis: Found that NSC could be isolated from the CNS
Hypothesis: Have shown that NSCs can differentiate into mature Oligodendrocytes in
animals. Found that NSC is self-renewing and showed benefits of healing other diseases.
Hypothesis: Other types of NSCs are Neural Progenitor Cells (NPCs) which have the
capability to differentiate into Oligodendrocytes and also have anti-inflammatory
properties such as cytokines and neutrophils. Those properties make NSC suitable for
cellular therapy in the brain.
Conclusions: Neural Stem Cells not only could be a cure for MS but also beneficial for
Huntington’s disease, Parkinson’s disease as well as Stroke, Spinal Cord injuries and
Amyotrophic Lateral Sclerosis.
Article #2: Mesenchymal Stem Cells as a Therapeutic Strategy for MS
Purpose of the study: Experimental and clinical use of bone marrow stem cells and the
possible mechanisms in the treatment of MS.
Methods: (Use of bone marrow, amniotic fluid, deciduous teeth, adipose tissue, umbilical
cord, synovial membranes, peripheral blood).
24 Mesenchymal Stem Cell – From both human and mouse
Results: Show that MSC upgrades the endogenous re-myelinating cells to participate
directly in myelination. It is suggested that genetic modification of MSCs could be a
potential therapeutic approach for elevating the efficacy of such treatment for MS and
other neurodegenerative diseases.
Hypothesis: Found that MSCs have a potential for migration into inflamed CNS tissue and
differentiate into cells expressing neuronal and glial cell markers.
Hypothesis: Found that they showed improvement in neurological functions compared
with controls, and suggested that MSCs can influence the rate of repair.
Hypothesis: Investigated potential role of MSCs on promotion of repair and recovery after
intrathecal injection into mice and intravenously in patients with MS. They showed a
clinical improvement in treating MS patients.
Conclusions: MSCs are capable of trans-differentiation into cells of the endodermal and
ectodermal origin which are confirmable with molecular, biomedical, anatomical and
electrophysiological characteristics. Through effects on endogenous progenitors in the
spinal cords, it is concluded that MSCs can be used in MS patients for promoting CNS
repair.
Article #3: Hematopoietic Stem Cell Transplantation in MS
Purpose of the study: The use of Hematopoietic Stem Cell Transplantation in the treating
MS by reducing the relapse rate and slowing the progression.
Methods: (Immunomodulatory therapy for the underlying immune disorder and therapies
to relieve or modify symptoms of MS).
48 Hematopoietic Stem Cell, 3 Embryonic Stem Cell
Results: Animal models of MS and humans, both revealed that HSC transplantation can
induce MS. Clinical and neurological outcomes after autologous HSC transplantation in 22
patients, showed that it can improve or stabilize neurological manifestations with
progressive MS, following failure of conventional therapy.
Hypothesis: Experimental autoimmune encephalomyelitis (EAE)-diseased mice have
shown that allogeneic HSC transplantation during acute phase of MS lead to full remission.
Moreover, autologous HSC transplantation in EAE mice resulted in complete remission.
Hypothesis: Some hematopoietic cells are recruited to sites of neurological damage to
become functional perivascular macrophage and microglia like dells. Although
macrophages play harmful or beneficial roles in CNS injury, they are able to remove the
cellular debris in the acute phase of injury.
Hypothesis:
Conclusions: The outcomes of 15 patients with progressive MS and a median EDSS of 6.0
by HSC transplantation after conditioning. During 6 months of follow- up, no death and
worsening of neurological symptoms were observed and EDSS was improved in 7 of 15
patients. But, results suggest that HSC transplantation could improve MS symptoms in
progressive phase.
Relatively young patients with active inflammatory lesions of relatively short duration and
rapidly progressive disease, but still low disability scores, unresponsive to conventional
therapy seem the best candidates for transplantation
Article #4: Embryonic Stem Cell Application in MS Treatment
Purpose of the study: Getting tissue-specific progenitor cells from human embryonic stem
cells in treating MS.
Methods: (ESCs are pluripotent stem cells that derived from the inner cell mass of an early
stage embryo called blastocyst and can be developed into any type of cell in the body and
ultimately a treatment for MS).
3 Embryonic Stem Cell
Results: Only three studies were reviewed in detail on the use of Embryonic stem cells
(ESCs) in MS. It was discovered that several systems such as small molecules and specific
transcription factors that control ESC fate produce neurons and oligodendrocytes. ESC-
derived oligodendrocytes are capable of re-myelination.
Hypothesis: Found to differentiate mouse embryonic stem cells (mESCs) into
oligodendrocytes with melogenic properties have revealed that ESCs can be directed into
neural cells.
Hypothesis: ESC-based therapies can give rise to specific specialty cells such as,
dermatomes from undifferentiated ESCs or incompletely differentiated neural cells.
Hypothesis: Found that transplanted ESC-derived neural progenitors into the mice with
EAE. They observed that clinical symptoms of EAE remarkably reduced after
transplantation. Histological evaluation revealed that transplanted neural progenitors
migrate to the mice brain, especially in the host white matter.
Conclusions: Stem cell therapy in axonal demyelination and neurological disability
(Specially MS) has accelerated growth in animal model as well as human patient clinical
treatment. A new way that promotes this procedure is tissue engineering which uses
synthesis of natural polymer that simulates extra cellular matrix for better response of the
body to grafted cells.
Article #5: Autologous Hematopoietic Stem Cell Transplantation (AHSCT) to treat MS
Purpose of the study: Support the feasibility of AHSCT with reduced-intensity
conditioning in MS.
Methods: Autologous Peripheral Blood Stem Cell Transplantation (APBCST)
Human
Results: AHSCT is a feasible treatment for severe MS and its long-term efficacy is
favorable. Patients with relapse have a good response to autologous AHSCT
transplantation, as a viable therapeutic option. AHSCT can be an effective treatment
option for this relatively rare disease course in MS.
Hypothesis: This study shows that AHSCT with a BEAM/ATG conditioning regimen has a
sustained effect in suppressing disease progression in aggressive MS cases unresponsive to
conventional therapies.
Hypothesis: Use of HDC-AHSCT could be effective and safe, but the very long-term risk of
adverse events due to sequential aggressive immune-suppression has to be established.
Hypothesis: Patients with secondary progressive MS refractory to conventional medical
treatment have longer progression-free survival following autologous stem cell
transplantation with intermediate-intensity conditioning regimens than with high-intensity
conditioning regimens.
Conclusions: AHSCT represents a viable and effective treatment option for aggressive
multiple sclerosis. After AHSCT, the rate of brain tissue loss in patients with MS declines
dramatically after the first 2 years. Cases with very active, relapsing-remitting (RRMS),
who underwent AHSCT, and obtained a dramatic resolution to disease activity is
associated with a long lasting suppression of inflammation and to a marked decrease of the
rate of brain atrophy after the second year following treatment.
Evaluation of the articles: All five articles' main objectives were to study the feasibility of
Stem Cell Therapy in Multiple Sclerosis and whether they were effective and how. Their
methodology was consistent among mouse and human. They also detailed a conclusive
result for each study.
Article #1 detailed that Neural Stem Cells (NSCs) could pave the road as a cure for the
treatment of MS. It also indicated that NSC could be beneficial for other diseases such as:
Huntington, Parkinson, Stroke, Spinal Cord injuries and Amyotrophic Lateral Sclerosis.
However, even with this success a lot of work still needs to be done to prove their clinical
effectiveness and safety.
Article #2 detailed that Mesenchymal Stem Cells (MSC) could be a viable option for MS.
This method uses bone marrow and amniotic fluid and therefore its positive effects through
endogenous progenitors in the spinal cord. It is concluded that MSCs can be used in MS
patient for promoting CNS repair.
Article #3 detailed that Hematopoietic Stem Cell Transplantation can be used to reduce the
relapse rate and slowing the progression in MS. The clinical study showed that it can
improve or stabilize neurological manifestations with progressive MS, following failure of
conventional therapy. The main findings were that young patients with active
inflammatory lesions of relatively short duration and rapidly progressing of the disease,
seemed to be the best candidates for transplantation. Although it is important to note that
HSC transplantation could improve MS symptoms only in the progressive phase.
Article #4 detailed that Embryonic Stem Cell Application (ESM) which are stem cells that
are taken from the inner cell mass of a blastocyst, an early stage embryo and can be
developed into any type of cell in the body. It was found that ESM stimulates extracellular
matrix for better response of body to grafted cells and are capable of re-myelination and
ultimately a treatment for MS.
Article #5 detailed that Autologous Hematopoietic Stem Cell Transplantation (AHSCT) I a
feasible treatment for severe MS. The study showed that patients with relapse have
received favorable long term responses. AHSCT represents a viable and effective
treatment option for aggressive multiple sclerosis.
After a fully, in-depth look at each study and its viable results outcome. I believe that the
best option for treating MS at an early stage is the Embryonic Stem Cell (ESM) because it
induces grafted cells that reverses myelination. However for patients with a more
progressive form of the disease, and who have had relapses, I believe that the best
treatment is the Autologous Hematopoietic Stem Cell Transplantation (AHSCT) because it
reduces the rate of brain tissue loss in patients dramatically after the first 2 years decrease
rate of brain atrophy. AHSCT transplantation showed to have long-term efficacy and a
favorable, viable therapeutic option. Alternative, Hematopoietic Stem Cell is the best
method for reducing the relapse rate and slowing the progression in MS in young patients
with active inflammatory lesions of relatively short duration and rapidly progressing of the
disease.
Feasibility of Cell Therapy in Multiple Sclerosis: A Systematic Review of 83 Studies
Abdolreza Ardeshiry lajimi, Majid Farshdousti Hagh, Najmaldin Saki, Esmaeil Mortaz,
Masoud Soleimani, Fakher Rahim
Int J Hematol Oncol Stem Cell Res. 2013; 7(1): 15–33.
PMCID:
PMC3913133
Article PubReader PDF–649KCitation
Is Cited by the Following 11 Articles in this Archive:
Differentiation of Human Mesenchymal Stem Cells towards Neuronal Lineage: Clinical
Trials in Nervous System Disorders
Rosa Hernández, Cristina Jiménez-Luna, Jesús Perales-Adán, Gloria Perazzoli,
Consolación Melguizo, José Prados
Biomol Ther (Seoul) 2020 Jan; 28(1): 34–44. Published online 2019 Oct 25. doi:
10.4062/biomolther.2019.065
PMCID:
PMC6939692
Article PubReader PDF–2.3MCitation
Stem cell therapy for multiple sclerosis
Fakher Rahim, Babak Arjmand, Roshanak Tirdad, Amal Saki Malehi
Cochrane Database Syst Rev. 2019 Sep; 2019(9): CD013049. Published online 2019 Sep 24.
doi: 10.1002/14651858.CD013049.pub2
PMCID:
PMC6759045
Currently embargoed: Free in PMC on Sep 24, 2020
Stem cell therapy for multiple sclerosis
Fakher Rahim, Babak Arjmand, Roshanak Tirdad, Amal Saki Malehi
Cochrane Database Syst Rev. 2018 Jun; 2018(6): CD013049. Published online 2018 Jun 11.
doi: 10.1002/14651858.CD013049
Update in:
Cochrane Database Syst Rev. 2019 Sep; 2019(9): CD013049.
PMCID:
PMC6513392
Article PubReader PDF–206KCitation
Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment
of multiple sclerosis
Neil H. Riordan, Isabela Morales, Giselle Fernández, Nicole Allen, Neal E. Fearnot,
Michael E. Leckrone, Dedra Jones Markovich, Darla Mansfield, Dorita Avila, Amit N.
Patel, Santosh Kesari, Jorge Paz Rodriguez
J Transl Med. 2018; 16: 57. Published online 2018 Mar 9. doi: 10.1186/s12967-018-1433-7
PMCID:
PMC5845260
Article PubReader PDF–2.0MCitation
A review on stem cell therapy for multiple sclerosis: special focus on human embryonic
stem cells
Geeta Shroff
Stem Cells Cloning. 2018; 11: 1–11. Published online 2018 Feb 12. doi:
10.2147/SCCAA.S135415
PMCID:
PMC5813951
Article PubReader PDF–1.2MCitation
Feasibility and toxicity of hematopoietic stem cell transplant in multiple sclerosis
Thomas Low Tat Kuan, Farahnaz Amini, Marjan Sadat Seghayat
Iran J Basic Med Sci. 2017 Jul; 20(7): 729–738. doi: 10.22038/IJBMS.2017.9000
PMCID:
PMC5569597
Article PubReader PDF–1.0MCitation
Autologous hematopoietic stem cell transplantation in progressive severe multiple sclerosis
Awadh Kishor Pandit, Kameshwar Prasad, Tulika Seth
Ann Indian Acad Neurol. 2015 Oct-Dec; 18(4): 459–463. doi: 10.4103/0972-2327.165482
PMCID:
PMC4683892
Article PubReaderCitation
Mesenchymal Stem Cells and Induced Pluripotent Stem Cells as Therapies for Multiple
Sclerosis
Juan Xiao, Rongbing Yang, Sangita Biswas, Xin Qin, Min Zhang, Wenbin Deng
Int J Mol Sci. 2015 May; 16(5): 9283–9302. Published online 2015 Apr 24. doi:
10.3390/ijms16059283
PMCID:
PMC4463588
Article PubReader PDF–1.0MCitation
Stem cell-based approach for the treatment of Parkinson's disease
Parisa Goodarzi, Hamid Reza Aghayan, Bagher Larijani, Masoud Soleimani, Ahmad-Reza
Dehpour, Mehrnaz Sahebjam, Firoozeh Ghaderi, Babak Arjmand
Med J Islam Repub Iran. 2015; 29: 168. Published online 2015 Jan 28.
PMCID:
PMC4431356
Article PubReader PDF–916KCitation
Comparison of osteogenic differentiation potential of human adult stem cells loaded on
bioceramic‐coated electrospun poly (L‐lactide) nanofibres
A. Ardeshirylajimi, M. Mossahebi‐Mohammadi, S. Vakilian, L. Langroudi, E. Seyedjafari,
A. Atashi, M. Soleimani
Cell Prolif. 2015 Feb; 48(1): 47–58. Published online 2014 Dec 11. doi: 10.1111/cpr.12156
PMCID:
PMC6496866
Article PubReader PDF–1.7MCitation
Comparison of random and aligned PCL nanofibrous electrospun scaffolds on
cardiomyocyte differentiation of human adipose-derived stem cells
Raheleh Safaeijavan, Masoud Soleimani, Adeleh Divsalar, Akram Eidi, Abdolreza
Ardeshirylajimi
Iran J Basic Med Sci. 2014 Nov; 17(11): 903–911.
PMCID:
PMC4328100
Article PubReader PDF–1.9MCitation
