Mesenchymal stem cells for ALS patients

Article (PDF Available)inAmyotrophic Lateral Sclerosis 10(2):123-4 · January 2009with47 Reads
DOI: 10.1080/17482960802572707 · Source: PubMed
COMMENTARY
Mesenchymal stem cells for ALS patients
LETIZIA MAZZINI
1
, ALESSANDRO VERCELLI
2
, KATIA MARESCHI
3
,
IVANA FERRERO
3
, LUCIA TESTA
1
& FRANCA FAGIOLI
3
1
Department of Neurology, Eastern Piedmont University, Maggiore della Carita
`
Hospital, Novara,
2
Department of
Anatomy, Pharmacology and Forensic Medicine, University of Torino, and
3
Stem Cell Transplantation and Cellular
Therapy Unit Paediatric Onco-Haematology Department, Regina Margherita Children’s Hospital, Torino, Italy
Badayan and Cudkowicz’s commentary article on
our recent paper published in the Journal of the
Neurological Sciences entitled ‘Stem cell treatment
in amyotrophic lateral sclerosis’ (1) raises some
important questions relative to the results and the
design of our trial in view of the possible outcome of
the treatment. The following comments should serve
to clarify the points mentioned:
1. The trial reported in our paper is a phase I
clinical trial that was designed to test the
safety and the feasibility of mesenchymal stem
cell transplantation into the spinal cord of
ALS patients. The inclusion criteria of the
patients and the monitoring instruments had
been selected to limit the impact of side-
effects or the damage related to cell trans-
plantation on the functional compliance of
patients. For this reason, all patients chosen
had already severe ambulation difficulties or
were wheelchair-bound at entry: FVC was
considered a main clinical monitoring para-
meter and the results were shown in the
figure. The treatment was practised in a
wide age-range because of the different age-
dependent cell growth potential or tolerability
of the surgical approach and anaesthesia.
With reference to the conclusions of the
authors, we wish to clarify that patients have
been recruited and treated in a tertiary ALS
centre by neurologists who have long-term
experience in the management of ALS pa-
tients and in managing clinical trials.
2. We are aware that, given the low number of
patients and the great variability in terms
of age and ALS parameters, no definite
conclusion is possible. However, to increase
the amount of data the Italian Institute of
Health approved a new phase I clinical trial
that was then performed in a further 10
patients. The data of this new study confirm
the safety of the procedure and the results will
be published soon.
3. We chose to inject different amounts of cells
because it was quite unreliable to determine
the optimal dose in animals and transpose it to
humans. Moreover, a single dose could miss
adverse events that could emerge in later trials
or large effects such as those observed in the
pharmacological clinical trials (2).
4. In patients who died during the follow-up,
necroscopy was not performed because of
refusal by relatives. Moreover, as MSCs were
not labelled, it would have been impossible to
verify the survival and the migration into the
spinal cord of patients.
5. Over the last two years our group has pub-
lished pre-clinical data which demonstrate
that MSCs might have a clinical use as for
cell based therapy in amyotrophic lateral
sclerosis.
. We previously reported that human
MSCs in a new culture condition existing
in a neural progenitor maintenance med-
ium (NPMM), acquired new morpholo-
gical characteristics, neural markers, and
electrophysiological properties, which are
suggestive of neural differentiation (3).
. We also demonstrated that expanded
MSCs can survive and migrate after
Correspondence: L. Mazzini, Department of Neurology, Eastern Piedmont University, Maggiore della Carita` Hospital, Novara 20100, Italy.
E-mail: mazzini.l@libero.it
(Received 20 October 2008; accepted 21 October 2008)
Amyotrophic Lateral Sclerosis. 2009; 10: 123124
ISSN 1748-2968 print/ISSN 1471-180X online # 2009 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)
DOI: 10.1080/17482960802572707
Amyotroph Lateral Scler Downloaded from informahealthcare.com by 157.122.192.59 on 05/20/14
For personal use only.
transplantation in the lumbar spinal cord
of SOD1-G93A mice, where they prevent
astrogliosis and microglial activation and
delay ALS-related decrease in the number
of motor neurons, resulting in an ameli-
oration of motor performance (4,5).
. MSCs isolated from bone marrow of ALS
patients maintain all their peculiar char-
acteristics and their extensive in vitro
expansion does not involve any function-
al modification including chromosomal
alterations or cellular senescence. More-
over, they acquire, under specific condi-
tions, new morphological characteristics
and neural markers that are suggestive
of neural differentiation as in healthy
donors (6).
Even though many questions regarding ALS remain
open, we think our study shows that autologous cell
therapy is feasible in ALS patients: MSCs are good
candidates for stem cell therapy in ALS.
References
1. Mazzini L, Mareschi K, Ferrero I, Vassallo E, Oliveri G,
Nasuelli N, et al. Stem cell treatment in amyotrophic lateral
sclerosis. Journal of the Neurological Sciences. 2008;265:
7883.
2. Allitia B, DiBernardo AB, Cudkowicz ME. Translating pre-
clinical insights into effective human trials in ALS. Biochimica
et Biophysica Acta. 2006;1762:113949.
3. Mareschi K, Novara M, Rustichelli D, Ferrero I, Guido D,
Carbone E, et al. Neural differentiation of human mesench-
ymal stem cells: evidence for expression of neural markers and
eag K channel types. Exp Hematol. 2006;34:156372.
4. Vercelli A, Garbossa D, Mereuta M, Muraca G, Mareschi K,
Rustichelli D, et al. Transplantation of human mesenchymal
stem cells into the lumbar spinal cord of G93A mice. Forum
European Neuroscience Vienna; 2006.
5. Vercelli A, Mereuta OM, Garbossa D, Muraca G, Mareschi K,
Rustichelli D, et al. Human mesenchymal stem cell transplan-
tation extends survival, improves motor performance and
decreases neuroinflammation in mouse model of amyotrophic
lateral sclerosis. Neurobiol Dis. 2008;31:395405.
6. Ferrero I, Mazzini L, Rustichelli D, Gunetti M, Mareschi K,
Testa L, et al. Bone marrow mesenchymal stem cells from
healthy donors and sporadic amyotrophic lateral sclerosis
patients. Cell Transplant. 2008;17:25566.
124 L. Mazzini et al.
Amyotroph Lateral Scler Downloaded from informahealthcare.com by 157.122.192.59 on 05/20/14
For personal use only.
    • "Research and clinical trials have been conducted to investigate the inhibitory effects of MSC transplantation on graft-versus-host disease (GVHD) after allogeneic tissue transplantation, rheumatism, uveitis, diabetes, and inflammatory bowel disease [29]. Furthermore, via their neuroprotective effects, MSCs can prevent amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, and glaucoma3031323334. As noted above, MSCs have multiple functions that include tissue repair, immunosuppression, and neuroprotection, but the mechanisms underlying these functions remain largely unknown. "
    [Show abstract] [Hide abstract] ABSTRACT: Many types of cells release phospholipid membrane vesicles thought to play key roles in cell-cell communication, antigen presentation, and the spread of infectious agents. Extracellular vesicles (EVs) carry various proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs), like a “message in a bottle” to cells in remote locations. The encapsulated molecules are protected from multiple types of degradative enzymes in body fluids, making EVs ideal for delivering drugs. This review presents an overview of the potential roles of EVs as natural drugs and novel drug-delivery systems.
    Full-text · Article · Feb 2016
    • "A trial in 2012 by the same group on 19 patients with ALS demonstrated that direct injection of MSCs into the thoracic spinal cord was safe. And this study is the first to show the safety of MSC transplantation in the central nervous system after a long time monitoring of nearly 9 years, and is in support of using MSCbased cellular therapy for neurodegenerative disorders2829303132 ( Challenges "
    [Show abstract] [Hide abstract] ABSTRACT: Motor Neuron disease is a neurodegenerative disease of central nervous system leading to death of motor neurons from CNS and spinal cord. Due to the lack of effective treatment modalities, recently, many scientists have considered stem cells as a potential strategy for the treatment of this disease. Amongst the different types of stem cells, MSCs have been thought as a promising source of stem cells in regenerative medicine applications. These cells can be transplanted into the injured nervous system as a new therapeutic strategy. Although many challenges and concerns still remain, and the exact mechanism by which stem cells act is still unknown, the positive effect of stem cells following transplantation has encouraged many researchers to consider this as a treatment option in the future. There has been a lot of research ongoing on the derivation of motor neurons from stem cells in vitro and many scientists are attempting to bring these cells into clinical applications by conducting a number of clinical trials. Here, in this review, we discuss the current progress in pre-clinical studies and the status of clinical trials using stem cells in motor neuron diseases. We also discuss the hurdles which need to be overcome while moving from bench to bedside. Based on current information available, stem cell derived motor neurons can pave the way as a new treatment option for patients with the disease which seems to be highly promising.
    Full-text · Article · Jan 2015 · International Journal of Molecular Sciences
    • "A trial in 2012 by the same group on 19 patients with ALS demonstrated that direct injection of MSCs into the thoracic spinal cord was safe. And this study is the first to show the safety of MSC transplantation in the central nervous system after a long time monitoring of nearly 9 years, and is in support of using MSCbased cellular therapy for neurodegenerative disorders2829303132 ( Challenges "
    [Show abstract] [Hide abstract] ABSTRACT: Motor Neuron disease is a neurodegenerative disease of central nervous system leading to death of motor neurons from CNS and spinal cord. Due to the lack of effective treatment modalities, recently, many scientists have considered stem cells as a potential strategy for the treatment of this disease. Amongst the different types of stem cells, MSCs have been thought as a promising source of stem cells in regenerative medicine applications. These cells can be transplanted into the injured nervous system as a new therapeutic strategy. Although many challenges and concerns still remain, and the exact mechanism by which stem cells act is still unknown, the positive effect of stem cells following transplantation has encouraged many researchers to consider this as a treatment option in the future. There has been a lot of research ongoing on the derivation of motor neurons from stem cells in vitro and many scientists are attempting to bring these cells into clinical applications by conducting a number of clinical trials. Here, in this review, we discuss the current progress in pre-clinical studies and the status of clinical trials using stem cells in motor neuron diseases. We also discuss the hurdles which need to be overcome while moving from bench to bedside. Based on current information available, stem cell derived motor neurons can pave the way as a new treatment option for patients with the disease which seems to be highly promising.
    Full-text · Article · Jan 2015 · International Journal of Molecular Sciences
Show more

    Recommended publications

    Discover more