Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Idiopathic Parkinson's Disease

Adverse events include renal failure, liver failure, and hemolytic anemia.

Adverse events include renal failure, liver failure, and hemolytic anemia.

Adverse events include renal failure, liver failure, and hemolytic anemia.

Adverse events include renal failure, liver failure, and hemolytic anemia.

The UPDRS serves as a disability and impairment scale for progression follow-up and is divided into four sections.

• Part I: evaluation of mentation, behavior, and mood (13 questions).
• Part II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions).
• Part III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores)
• Part IV: motor complications (6 questions)

All items have 5 response options with uniform anchors of: 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/signs that prevent function).

The UPDRS serves as a disability and impairment scale for progression follow-up and is divided into four sections.

• Part I: evaluation of mentation, behavior, and mood (13 questions).
• Part II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions).
• Part III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores)
• Part IV: motor complications (6 questions)

All items have 5 response options with uniform anchors of: 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/signs that prevent function).

The UPDRS serves as a disability and impairment scale for progression follow-up and is divided into four sections.

• Part I: evaluation of mentation, behavior, and mood (13 questions).
• Part II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions).
• Part III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores)
• Part IV: motor complications (6 questions)

All items have 5 response options with uniform anchors of: 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/signs that prevent function).

The UPDRS serves as a disability and impairment scale for progression follow-up and is divided into four sections.

• Part I: evaluation of mentation, behavior, and mood (13 questions).
• Part II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions).
• Part III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores)
• Part IV: motor complications (6 questions)

All items have 5 response options with uniform anchors of: 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/signs that prevent function).

Parts III and IV of the UPDRS will be performed as described above.

Parts III and IV of the UPDRS will be performed as described above.

Parts III and IV of the UPDRS will be performed as described above.

Parts III and IV of the UPDRS will be performed as described above.

Time in seconds required to stand from a chair, walk 7meters, turn, walk back to the chair and sit down.

Time in seconds required to stand from a chair, walk 7meters, turn, walk back to the chair and sit down.

Time in seconds required to stand from a chair, walk 7meters, turn, walk back to the chair and sit down.

Time in seconds required to stand from a chair, walk 7meters, turn, walk back to the chair and sit down.

The Modified Hoehn and Yahr Scale is a staging instrument that defines broad categories of motor function in Parkinson's disease, starting at Stage 0: no signs of disease to the highest stage 5: wheelchair bound or bedridden unless aided.

The Modified Hoehn and Yahr Scale is a staging instrument that defines broad categories of motor function in Parkinson's disease, starting at Stage 0: no signs of disease to the highest stage 5: wheelchair bound or bedridden unless aided.

The Modified Hoehn and Yahr Scale is a staging instrument that defines broad categories of motor function in Parkinson's disease, starting at Stage 0: no signs of disease to the highest stage 5: wheelchair bound or bedridden unless aided.

The Modified Hoehn and Yahr Scale is a staging instrument that defines broad categories of motor function in Parkinson's disease, starting at Stage 0: no signs of disease to the highest stage 5: wheelchair bound or bedridden unless aided.

Diffusion tensor and T2 imaging with the resting state functional connectivity technique will be used.

Resting cerebral blood flow (CBF) will be measured using a pseudo-continuous arterial spin labeling (pCASL) MRI sequence with gradient-echo echo-planar imaging (EPI), which allows for a non-invasive quantification of CBF.

A set of diffusion-weighted image volumes (32-directions, high angular resolution) will be collected using the gradient overplus option with one B0 (non-diffusion weighted) image volume acquired before the acquisition of one repetition of the diffusion-weighted scans. Diffusion tensor and associated computations will be performed. White matter microstructure will be examined, which represents the structural pathways linking specific cortical and subcortical regions. It will be determined whether there is increased fractional anisotropy and decreased mean diffusivity along white matter fibers that link regions exhibiting increased functional connectivity, such as substantia nigra and dorsal striatum.

Anatomical imaging allows visualization of the brain structure at the level of about 1 cubic millimeter. These scans will be used to estimate the volume of subcortical structures (e.g., putamen, caudate nucleus).

Anatomical imaging allows visualization of the brain structure at the level of about 1 cubic millimeter. These scans will be used to measure cortical thickness (e.g., gray matter density).

Anatomical imaging allows visualization of the brain structure at the level of about 1 cubic millimeter. These scans will be used to detect any gross structural changes or inflammation that appear during the course of treatment.

Whole-brain echo-planar imaging (EPI) runs sensitive to BOLD contrast will be acquired while participants do self-paced finger tapping using their left and right hands at separate points in time, and during the resting state after being instructed to remain still and fixate on a white crosshair displayed on a black background during the functional acquisition. Functional imaging will be done in the OFF medication state. It will be determined whether there is a reduction in the abnormally high activity pattern in motor cortex and an increase in putamen activity.

The Schwab & England scale is a physician assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson disease appeared. Scores range from 100% to 0% in increments of 10%, where 100% is completely independent and 0% is only vegetative functions.

The Schwab & England scale is a physician assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson disease appeared. Scores range from 100% to 0% in increments of 10%, where 100% is completely independent and 0% is only vegetative functions.

The Schwab & England scale is a physician assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson disease appeared. Scores range from 100% to 0% in increments of 10%, where 100% is completely independent and 0% is only vegetative functions.

The Schwab & England scale is a physician assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson disease appeared. Scores range from 100% to 0% in increments of 10%, where 100% is completely independent and 0% is only vegetative functions.

The PDQ-39 is a 39 questions Parkinson's Disease self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact QoL and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.

The PDQ-39 is a 39 questions Parkinson's Disease self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact QoL and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.

The PDQ-39 is a 39 questions Parkinson's Disease self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact QoL and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.

The PDQ-39 is a 39 questions Parkinson's Disease self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact QoL and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.

The Montreal Cognitive Assessment is a rapid screening instrument for working memory, visual-spatial abilities, executive function, attention, concentration, language and orientation. The total score ranges from 0 to 30; a score of 26 or above is considered normal.

Investigators will assess cytokines associated with inflammation [interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), Tumor Necrosis Factor beta (TNFβ)]; cell growth and differentiation [Brain-derived neurotrophic factor (BDNF), Granulocyte-macrophage colony-stimulating factor (GM-CSF)]; monocyte migration [Fractalkine, Eotaxin, monocyte chemotactic protein 1 (MCP-1), Macrophage Inflammatory Protein 1 beta (MIP-1β)]; and adaptive immune response [interleukin 12 subunit beta (IL-12p40), interleukin 7 (IL-7), interleukin 9 (IL-9), interleukin 4 (IL-4)] will be measured.

Investigators will assess cytokines associated with inflammation [interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), Tumor Necrosis Factor beta (TNFβ)]; cell growth and differentiation [Brain-derived neurotrophic factor (BDNF), Granulocyte-macrophage colony-stimulating factor (GM-CSF)]; monocyte migration [Fractalkine, Eotaxin, monocyte chemotactic protein 1 (MCP-1), Macrophage Inflammatory Protein 1 beta (MIP-1β)]; and adaptive immune response [interleukin 12 subunit beta (IL-12p40), interleukin 7 (IL-7), interleukin 9 (IL-9), interleukin 4 (IL-4)] will be measured.

Investigators will assess cytokines associated with inflammation [interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), Tumor Necrosis Factor beta (TNFβ)]; cell growth and differentiation [Brain-derived neurotrophic factor (BDNF), Granulocyte-macrophage colony-stimulating factor (GM-CSF)]; monocyte migration [Fractalkine, Eotaxin, monocyte chemotactic protein 1 (MCP-1), Macrophage Inflammatory Protein 1 beta (MIP-1β)]; and adaptive immune response [interleukin 12 subunit beta (IL-12p40), interleukin 7 (IL-7), interleukin 9 (IL-9), interleukin 4 (IL-4)] will be measured.

Investigators will assess cytokines associated with inflammation [interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), Tumor Necrosis Factor beta (TNFβ)]; cell growth and differentiation [Brain-derived neurotrophic factor (BDNF), Granulocyte-macrophage colony-stimulating factor (GM-CSF)]; monocyte migration [Fractalkine, Eotaxin, monocyte chemotactic protein 1 (MCP-1), Macrophage Inflammatory Protein 1 beta (MIP-1β)]; and adaptive immune response [interleukin 12 subunit beta (IL-12p40), interleukin 7 (IL-7), interleukin 9 (IL-9), interleukin 4 (IL-4)] will be measured.

The CSSRS rating scale is a set of questions directed towards eliciting verbalization of suicidal feelings or actions