Intrathecal administration of autologous mesenchymal stromal cells for spinal cord injury: Safety and efficacy of the 100/3 guideline

Ovejero, Mercedes; Vaquero, Jesús; Zurita, Mercedes; Bonilla, Celia; Rico, Miguel A.; Aguayo, Concepción; Rodríguez, Alicia; Martinez, P.; Calle, Silvia de la; Fernández, Marta V.; Fernández, Cecilia A.; Rodríguez-Boto, G.; Reina, Laura de; Saab, Anwar; Cotúa, Carlos; Santander, Xavier A.; Gutiérrez, Rodolfo Gozalo; Saldaña, Cristóbal; Hassan, Rasha Mahmoud; Ortega, Celia; Madrid, Alicia; Mariscal, Montaña; Marı́n, Esperanza; López, L.F Llopis; Pérez, Alberto; Ebrat, Edwin E.; Vaquero, Marta; Martin, Mark; Mayoral, I.; Canales, Dolores; Carballido, Joaquı́n; Vázquez, Diego García-Germán; Serrano, Rosario; Saucedo, Gertrudis; Tapiador, Noemi; Sevilla, Marta González; Cabrera, Rafael; Camino, Maria E. Martínez Begoña Pérez de; Alarcón, Ana; Naya, Daniel E.; Alonso, Rosalía; Alamo, Jose R.; Romera, Irene; Mourelle, Inmaculada; Sánchez, Carmen; Segovia, Rocío; Gutiérrez, Alberto; Guillo, Verónica; Valle, Sara Del; Rey, Paula Requeijo; Mucientes, Jorge; Rodríguez, B

doi:10.1016/j.jcyt.2018.03.032

Cited by 95 publications

(61 citation statements)

References 23 publications

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“…A dosage of 2 × 10 6 cells/kg body weight is commonly given to the patients [6,7]. For certain patients and diseases, multiple administrations of MSCs up to several hundred million cells are needed to achieve the desired therapeutic effect [11,12].…”

Section: Introductionmentioning

confidence: 99%

Large-Scale Expansion of Human Mesenchymal Stem Cells

Hassan

Yazid

Yunus

et al. 2020

Stem Cells International

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Mesenchymal stem cells (MSCs) are multipotent stem cells with strong immunosuppressive property that renders them an attractive source of cells for cell therapy. MSCs have been studied in multiple clinical trials to treat liver diseases, peripheral nerve damage, graft-versus-host disease, autoimmune diseases, diabetes mellitus, and cardiovascular damage. Millions to hundred millions of MSCs are required per patient depending on the disease, route of administration, frequency of administration, and patient body weight. Multiple large-scale cell expansion strategies have been described in the literature to fetch the cell quantity required for the therapy. In this review, bioprocessing strategies for large-scale expansion of MSCs were systematically reviewed and discussed. The literature search in Medline and Scopus databases identified 26 articles that met the inclusion criteria and were included in this review. These articles described the large-scale expansion of 7 different sources of MSCs using 4 different bioprocessing strategies, i.e., bioreactor, spinner flask, roller bottle, and multilayered flask. The bioreactor, spinner flask, and multilayered flask were more commonly used to upscale the MSCs compared to the roller bottle. Generally, a higher expansion ratio was achieved with the bioreactor and multilayered flask. Importantly, regardless of the bioprocessing strategies, the expanded MSCs were able to maintain its phenotype and potency. In summary, the bioreactor, spinner flask, roller bottle, and multilayered flask can be used for large-scale expansion of MSCs without compromising the cell quality.

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Section: Introductionmentioning

confidence: 99%

Large-Scale Expansion of Human Mesenchymal Stem Cells

Hassan

Yazid

Yunus

et al. 2020

Stem Cells International

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“…Variable pattern of recovery in Barthel Index. No significant changes in SEP, MEP and NCV [ 47 ] Chronic A, B, C and D 11 BM Intrathecal 3 × 10 8 BMSCs 3 (every 3 months) No AE Improvement in ASIA pin prick score, ASIA light touch score, ASIA motor score, IANR-SCIFRS score, VAS score and bladder function [ 48 ] Chronic A 14 BM Intraspinal 5 × 10 6 BMSCs/cm 3 lesion volume 1 No AE 7/12 patients showed improvement in AIS grade [ 49 ] Chronic A 40 BM Intraspinal 2 × 10 7 BMSCs 1 No AE 9/20 patients showed improvement in AIS grade from A to B [ 50 ] Chronic A, B and C 20 BM Intraspinal 1 × 10 8 BMSCs 1 No AE 4/8 (50%), 3/4 (75%) and 8/8 (100%) patients with AIS grade A, B and C respectively showed improvement in AIS grade [ 51 ] Subacute and chronic A, B and C 20 BM Intra-arterial and intravenous 104 ± 44.3 × 10 8 BMMCs 1 No AE Improvement in ASIA score in patient...…”

Section: Mesenchymal Stem Cell Therapy For Spinal Cord Injurymentioning

confidence: 99%

“…Besides, there were also no significant changes in SEP, motor evoked potentials (MEP) and nerve conduction velocity (NCV) as well as a variable pattern of recovery in Barthel Index. Vaquero et al [ 47 ] reported improvement in sensation, motor and bladder function, and IANR-SCIFRS score as well as a reduction in neuropathic pain in the chronic SCI patients (time of injury to participation 13.65 ± 14.79 years) received the BMSC therapy.…”

Section: Mesenchymal Stem Cell Therapy For Spinal Cord Injurymentioning

confidence: 99%

“…Ideally, a single administration of MSCs is sufficient to exert its regenerative effect. However, a significant number of clinical studies administered the cells multiple times to get positive results [ 7 , 40 , 41 , 44 , 46 , 47 , 53 , 61 , 64 ]. It is postulated that the transplanted cells only can survive for a limited period in the hostile environment.…”

Section: Criteria To Consider When Applying Mesenchymal Stem Cell Thementioning

confidence: 99%

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Treatment of spinal cord injury with mesenchymal stem cells

Liau

Looi²,

Chia³

et al. 2020

Cell Biosci

145

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Background Spinal cord injury (SCI) is the damage to the spinal cord that can lead to temporary or permanent loss of function due to injury to the nerve. The SCI patients are often associated with poor quality of life. Results This review discusses the current status of mesenchymal stem cell (MSC) therapy for SCI, criteria to considering for the application of MSC therapy and novel biological therapies that can be applied together with MSCs to enhance its efficacy. Bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (ADSCs) have been trialed for the treatment of SCI. Application of MSCs may minimize secondary injury to the spinal cord and protect the neural elements that survived the initial mechanical insult by suppressing the inflammation. Additionally, MSCs have been shown to differentiate into neuron-like cells and stimulate neural stem cell proliferation to rebuild the damaged nerve tissue. Conclusion These characteristics are crucial for the restoration of spinal cord function upon SCI as damaged cord has limited regenerative capacity and it is also something that cannot be achieved by pharmacological and physiotherapy interventions. New biological therapies including stem cell secretome therapy, immunotherapy and scaffolds can be combined with MSC therapy to enhance its therapeutic effects.

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“…MSCs have proven to be safe or exhibited clinical efficacy in the field of regenerative medicine. Examples include improving neurologic function in amyotrophic lateral sclerosis ( Petrou et al, 2016 ; Sykova et al, 2017 ; Berry et al, 2019 ), cerebral palsy ( Wang X. et al, 2013 ; Huang et al, 2018 ), delayed encephalopathy after carbon monoxide poisoning ( Wang H. et al, 2016 ), epilepsy ( Hlebokazov et al, 2017 ), stroke ( Bang et al, 2005 ; Lee et al, 2010 ), metachromatic leukodystrophy ( Koc et al, 2002 ), and spinal cord injury ( Vaquero et al, 2018 ); improved sexual function in erectile dysfunction ( Al Demour et al, 2018 ); improved motor activity with frailty disorder ( Tompkins et al, 2017 ), and multiple system atrophy ( Lee et al, 2008 , 2012 ; Singer et al, 2019 ); improved cardiovascular function in heart failure ( Hare et al, 2012 ; Golpanian et al, 2015 ; Mathiasen et al, 2015 ; Bartolucci et al, 2017 ), and myocardial ischemia/angina ( Hare et al, 2009 ; Friis et al, 2011 ; Haack-Sorensen et al, 2013 ; Karantalis et al, 2014 ; Kim et al, 2018 ), improved bone repair in hypophosphatasia ( Taketani et al, 2015 ), lumbar disc degeneration ( Orozco et al, 2011 ; Noriega et al, 2017 ), osteogenesis imperfecta ( Gotherstrom et al, 2014 ), and osteonecrosis ( Hernigou et al, 2018 ); improved healing from kidney injury ( Tan et al, 2012 ; Saad et al, 2017 ); improved healing from liver injury related to acute on chronic hepatitis ( Shi et al, 2012 ; Lin et al, 2017 ) and ischemic biliary lesions following liver transplantation ( Zhang et al, 2017 ); improved hematopoietic recovery ( Xiao et al, 2013 ; Zhang et al, 2013 ; Xiong et al, 2014 ); and accelerated wound healing ( Falanga et al, 2007 ). From these indications, remestemcel-L is already in phase III trials for advanced heart failure and chronic low back pain.…”

Section: Infusion Of Mscs For Tissue Repair and Regenerationmentioning

confidence: 99%

Mesenchymal Stromal Cells and Exosomes: Progress and Challenges

Forsberg

Kink

Hematti

et al. 2020

Front. Cell Dev. Biol.

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Due to their robust immunomodulatory capabilities, mesenchymal stem/stromal cells (MSCs) have been used as a cellular therapy for a number of human diseases. Part of the mechanism of action of MSCs is the production of extracellular vesicles (EVs) that contain proteins, nucleic acids, and lipids that transmit signals to recipient cells that change their biologic behavior. This review briefly summarizes the development of MSCs as a treatment for human diseases as well as describes our present understanding of exosomes; how they exert their effects on target cells, and how they are differentiated from other EVs. The current treatment paradigm for acute radiation syndrome (ARS) is discussed, and how MSCs and MSC derived exosomes are emerging as treatment options for treating patients after radiation exposure. Other conditions such as graftversus-host disease and cardiovascular disease/stroke are discussed as examples to highlight the immunomodulatory and regenerative capacity of MSC-exosomes. Finally, a consideration is given to how these cell-based therapies could possibly be deployed in the event of a catastrophic radiation exposure event.

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Intrathecal administration of autologous mesenchymal stromal cells for spinal cord injury: Safety and efficacy of the 100/3 guideline

Abstract: The present guideline for cell therapy is safe and shows efficacy in patients with SCI, mainly in recovery of sphincter dysfunction, neuropathic pain and sensitivity.

Cited by 95 publications

References 23 publications

Large-Scale Expansion of Human Mesenchymal Stem Cells

Large-Scale Expansion of Human Mesenchymal Stem Cells

Treatment of spinal cord injury with mesenchymal stem cells

Mesenchymal Stromal Cells and Exosomes: Progress and Challenges

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