Mesenchymal Stem Cells: A Potential Therapeutic Approach for Amyotrophic Lateral Sclerosis?

Table 2

Overview of the studies and clinical trials with available and published results involving the administration of MSCs in ALS patients.

NCT number/ethical approval	Clinical trial title	Phase	MSC source	MSC administration	Number of cells	Number of patients	Location	Major adverse events	Delayed disease progression	Ref.
NCT01759797	Intravenous Transplantation of Mesenchymal Stem Cell in Patients With ALS	Phase 1	Autologous BMMSCs	Intravenous	cells/kg	6	Iran	No	No	[70]
NCT01771640	Intrathecal Transplantation of Mesenchymal Stem Cell in Patients With ALS	Phase 1	Autologous BMMSCs	Intrathecal	cells/kg	8	Iran	No	No	[70]
NCT01363401	Safety and Efficacy Study of Autologous Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis	Phase 1/2	Autologous BMMSCs	Two repeated intrathecal injections	cells/kg, range 48- cells	8: phase 1; 64: phase 2	Korea	No	Yes	[71, 73]
NCT01609283	A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis	Phase 1	Autologous ADMSCs	Intrathecal	Group 1: cells; Group 2: cells; Group 3: cells (2 doses); Group 4: cells; Group 5: cells (2 doses)	27	United States	No	No	[74]
NCT01777646	Autologous Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in Patients With Amyotrophic Lateral Sclerosis (ALS)	Phase 2	BMMSCs induced to secrete neurotrophic factors	Both intramuscular and intrathecal	Low dose: cells/kg intrathecal and cells intramuscular; mid-dose: cells/kg intrathecal and cells intramuscular; and high dose: cells/kg intrathecal and cells intramuscular	14	Israel	No	Yes	[75]
NCT01051882	Autologous Cultured Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSCNTF), in ALS Patients.	Phase 1/2	BMMSCs induced to secrete neurotrophic factors	Intramuscular injections at 24 separate sites or intrathecal administration.	cells/site (intramuscular); /kg cells (intrathecal)	12	Israel	No	Yes	[75]
NCT02881476	Therapeutic Treatment of Amyotrophic Lateral Sclerosis	Phase 1	Allogeneic Wharton’s jelly-derived MSCs	Intrathecal	Average dose of cells/kg	43	Poland	No	—	[76]
NCT02881489	Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Patients With Amyotrophic Lateral Sclerosis (UwmBmmscALS)	Phase 1	Autologous BM-MSCs	Intrathecal	Mean:	30	Poland	No	Yes/no	[77]
Ethical Committee of the Piedmont Region	—	—	Autologous BMMSCs	Intraspinal	—	7	Italy	No	—	[78]
Ethical Committee of the Piedmont Region	—	—	Autologous BMMSCs	Intraspinal	Range: 7.0–	9	Italy	No	Yes	[79]
Ethical Committee of the Piedmont Region	—	—	Autologous BMMSCs	Intraspinal	Range: 7.0–	9	Italy	No	Yes	[80]
Registration number 16454-pre21-823; approved and monitored by the National Institute of Health and by the Ethics Committees of the Piedmont Region, the “Maggiore della Carità” and “San Giovanni Bosco” Hospitals	—	Phase 1	Autologous BMMSCs	Intraspinal	Range: 11.4- cells	10	Italy	No	—	[81]
Registration numbers 12947-29.3 and 16454-pre21-823; approved and monitored by the ethics committees of the Piedmont Region, ‘Maggiore della Carità’ and San Giovanni Bosco hospitals and the National Institute of Health, Rome	—	Phase 1	Autologous BMMSCs	Intraspinal	Range: –	19	Italy	No	No	[82]
Ethics committees of the Gennimatas General Hospital and Hadassah Hebrew University Hospital and registered in the National Institutes of Health database	—	Phase 1/2	Autologous BMMSCs	Intrathecal. 9 patients also received intravenous MSCs	Mean cells. 9 patients also received intravenous MSCs: mean	19	Israel	No	—	[83]
IRB (HYUH IRB 2006-339) and the Korean Food and Drug Association (KFDA, Bio-47)	—	—	Autologous BMMSCs	Intrathecal (two monthly doses)	cells per kg	37	South Korea	—	Yes/no	[84]
EudraCT No. 2011-000362-35; State Institute for Drug Control and by the ethics committee of the University Hospital Motol in Prague, Czech Republic	—	Phase 1/2a	Autologous BMMSCs	Intrathecal	cells	26	Czech Republic	No	Yes	[85]
This study was approved and supported by Shefa Neuroscience Research Center, Tehran, Iran (N.S.R.C.sh89-1).	—		Bone marrow-derived neural stem cells	Intraspinal	cells	8	Iran	No	Yes	[86]
Ethics Committee of Republican Research and Practical Center of Neurology and Neurosurgery	—	—	Autologous BMMSCs committed to neuronal differentiation	Intravenous. Neural induced MSC were injected via lumbar puncture	Untreated cells: 0.5-/kg body weight; range: 42-102 × 10^6 cells. Neural induced; MSCs: 5.0- cells	10	Belarus	No	Yes	[87]

ADMSCs: adipose derived mesenchymal stem cells; ALS: amyotrophic lateral sclerosis; BMMSCs: bone marrow mesenchymal stem cells; MSCs: mesenchymal stem cells; UC-MSCs: umbilical cord mesenchymal stem cells.