The use of mesenchymal stem cells (MSCs) for amyotrophic lateral sclerosis (ALS) therapy – a perspective on cell biological mechanisms

Tang, Bor Luen

doi:10.1515/revneuro-2017-0018

Cited by 14 publications

(9 citation statements)

References 168 publications

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“…AD [57,58] and MS [59] are two such devastating diseases. ALS and PD+ syndromes may also be autoimmune and inflammatory in nature, as may TBI or chronic traumatic encephalopathy (CTE) [21,60,61]. Of course, the second capability of stem cells, to actually regenerate dead or diseased neurons, also needed experimentation.…”

Section: Discussionmentioning

confidence: 99%

“…In another report, upregulation of glial-derived neurotrophic factor occurred, indicating a role in neuroprotection as well [72]. Indeed many experimental reports for using ADSCs for this disease exist [29,61,[73][74][75][76][77][78][79][80][81][82][83]. Of note, Habisch, et al [83]., reported the inefficacy in obtaining adequate stem cell levels in the brain parenchyma with intrathecal injection due to layering out secondary to the effect of gravity.…”

Section: Alsmentioning

confidence: 97%

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Human intracerebroventricular (ICV) injection of autologous, non-engineered, adipose-derived stromal vascular fraction (ADSVF) for neurodegenerative disorders: results of a 3-year phase 1 study of 113 injections in 31 patients

Duma¹,

Kopyov²,

Kopyov³

et al. 2019

Mol Biol Rep

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We have chosen to test the safety of human intracerebroventricular (ICV) brain injections of autologous non-geneticallymodified adipose-derived stromal vascular fraction (ADSVF). In this IRB-approved trial, 24 patients received ICV ADSVF via an implanted reservoir between 5/22/14 and 5/22/17. Seven others were injected via their ventriculo-peritoneal shunts. Ten patients had Alzheimer's disease (AD), 6 had amyotrophic lateral sclerosis (ALS), 6 had progressive multiple sclerosis (MS-P), 6 had Parkinson's "Plus" (PD+), 1 had spinal cord injury, 1 had traumatic brain injury, and 1 had stroke. Median age was 74 (range 41-83). Injections were planned every 2-3 months. Thirty-one patients had 113 injections. Patients received SVF injection volumes of 3.5-20 cc (median:4 cc) containing 4.05 × 10 5 to 6.2 × 10 7 cells/cc, which contained an average of 8% hematopoietic and 7.5% adipose stem cells. Follow-up ranged from 0 to 36 months (median: 9.2 months). MRIs post injection(s) were unchanged, except for one AD patient whose hippocampal volume increased from < 5th percentile to 48th percentile (NeuroQuant ® volumetric MRI). Of the 10 AD patients, 8 were stable or improved in tests of cognition. Two showed improvement in P-tau and ß-amyloid levels. Of the 6 MS-P patients all are stable or improved. Four of 6 ALS patients died of disease progression. Twelve of 111 injections (11%) led to 1-4 days of transient meningismus, and mild temperature elevation, which resolved with acetaminophen and/or dexamethasone. Two (1.8% of injections) required hospitalization for these symptoms. One patient (0.9% of injections) had his reservoir removed and later replaced for presumed infection. In this Phase 1 safety trial, ADSVF was safely injected into the human brain ventricular system in patients with no other treatment options. Secondary endpoints of clinical improvement or stability were particularly promising in the AD and MS-P groups. These results will be submitted for a Phase 2 FDA-approved trial.

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Section: Discussionmentioning

confidence: 99%

Section: Alsmentioning

confidence: 97%

Human intracerebroventricular (ICV) injection of autologous, non-engineered, adipose-derived stromal vascular fraction (ADSVF) for neurodegenerative disorders: results of a 3-year phase 1 study of 113 injections in 31 patients

Duma¹,

Kopyov²,

Kopyov³

et al. 2019

Mol Biol Rep

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“…Human MSC must meet the following three criteria: (i) adherence to plastic when maintained in culture; (ii) positive expression of several antigens such as CD90, CD105, and CD73; and (iii) ability to differentiate into osteoblasts, adipocytes, and chondrocytes under in vitro inductive conditions . Clinical trials are now being performed in patients with diseases including not only BPD but also graft‐versus‐host disease after BM transplantation, systemic lupus erythematosus, Crohn's disease, diabetes mellitus, multiple sclerosis, amyotrophic lateral sclerosis, spinal cord injury, and liver failure due to cirrhosis and hepatitis B …”

Section: What Are Msc?mentioning

confidence: 99%

Mesenchymal stem cells for the prevention of bronchopulmonary dysplasia

Namba

2019

Pediatrics International

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Bronchopulmonary dysplasia (BPD) is a chronic lung disease in preterm infants who have been treated with supplemental oxygen and mechanical ventilation. Despite major advances in perinatal and neonatal medicine, limited progress has been made in reducing BPD rates. The use of mesenchymal stem cells (MSC) is a promising and innovative therapy for several diseases because they are easy to extract and they have low immunogenicity, anti-inflammatory properties, and regenerative ability. According to several pre-clinical studies that have used BPD animal models, one mechanism of action for MSC in BPD is mainly due to the paracrine effects of MSC-derived humoral factors, such as interleukin (IL)-6, IL-8, vascular endothelial growth factor, collagen, and elastin, rather than the multilineage and regenerative capacities of MSC. Cell-free preparations derived from MSC, including conditioned media and exosomes, remain a pre-clinical technology despite their great clinical potential. A first-in-human clinical trial of MSC treatment for BPD was performed as a phase I dose-escalation trial using umbilical cord blood-derived MSC. That trial demonstrated the short-and long-term safety and feasibility of MSC, given that significantly reduced inflammatory marker expression was observed in tracheal aspirates. As of recently, several clinical trials of MSC use for BPD are ongoing or are planned in some countries to investigate the efficacy of MSC in the prevention or treatment of BPD in premature infants. Many clinicians are currently awaiting the results from these trials so that MSC can be used clinically for human BPD. 100 Unknown Cord blood Recruiting BPD, bronchopulmonary dysplasia; FiO 2 , fraction of inspired oxygen; MSC, mesenchymal stem cells.

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“…Several studies explored the therapeutic potential of MSCs in ALS models. These studies delivered MSCs to diseased animal through various routes, local and systemic, including intraspinal, intrathecal, intramuscular, and intravenous [137][138][139][140].…”

Section: Preclinical Studies Using Human Mesenchymal Stem Cellsmentioning

confidence: 99%

Astrocytes in Pathogenesis of ALS Disease and Potential Translation into Clinic

Izrael¹,

Guy²,

Itskovitz‐Eldor³

et al. 2018

Astrocyte - Physiology and Pathology

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Astrocytes are the major cell population in the central nervous system (CNS) and play pivotal role in CNS homeostasis and functionality. Malfunction of astrocytes were implicated in multiple neurodegenerative diseases and disorders, including amyotrophic lateral sclerosis (ALS), spinal cord injury (SCI), brain stroke, Parkinson's disease (PD), and Alzheimer disease (AD). These new insights led to the rationale that transplantation of healthy and functional human astrocytes could support survival of neurons and be of therapeutic value in treating neurodegenerative diseases. Here, we will mainly focus on the role of astrocytes in ALS disease, the major cell sources for generation of human astrocytes, or astrocyte like cells and show how multiple preclinical studies demonstrate the efficacy of these cells in animal models. In addition, we will cover immerging early stage clinical trials that are currently being conducted using human astrocytes or human astrocyte like cell population.

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The use of mesenchymal stem cells (MSCs) for amyotrophic lateral sclerosis (ALS) therapy – a perspective on cell biological mechanisms

Cited by 14 publications

References 168 publications

Human intracerebroventricular (ICV) injection of autologous, non-engineered, adipose-derived stromal vascular fraction (ADSVF) for neurodegenerative disorders: results of a 3-year phase 1 study of 113 injections in 31 patients

Human intracerebroventricular (ICV) injection of autologous, non-engineered, adipose-derived stromal vascular fraction (ADSVF) for neurodegenerative disorders: results of a 3-year phase 1 study of 113 injections in 31 patients

Mesenchymal stem cells for the prevention of bronchopulmonary dysplasia

Astrocytes in Pathogenesis of ALS Disease and Potential Translation into Clinic

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