Lower Limb and Walking

Cellular Transplantation Therapies to Augment Strength and Walking Function

Experimental animal research utilizing stems cells and other cells or tissue to treat severe spinal cord injury is now being translated to human clinical studies. Recent reports have explored the feasibility of using cellular transplantation therapies (autologous bone marrow MSCs or OMA) to help increase function and reduce impairments in people with chronic SCI, but further studies are needed to determine safety, dosage, and timing before these treatments should be offered to patients.

Table 21. Cellular Transplantation Therapies to Augment Strength and Walking Function

Author Year; Country Score Research Design ample Size	Methods	Outcomes
Kishk et al. 2010; Egypt Case Control Level 3 N=64	Population: Treated Group – 36 males, 7 females; mean (SD) age 31.7(10.4); 12 complete, 31 incomplete SCIControl Group – 15 males, 5 females; mean (SD) age 33.8(11.8); 3 complete, 17 incomplete SCI Treatment: Monthly intrathecal injection of autologous bone marrow MSCs for 6 months, all participants received 3 rehabilitation therapies per week. Outcome Measures: Trunk muscle assessment, MASS, Functional Ambulation Categories, AIS sensorimotor, motor and sensory scores, lower-limb somatosensory evoked potentials (SSEPS)	A significantly greater proportion of the treatment group showed improved motor scores, but this is not clinically relevant as it was only by 1-2 points in 18/44 participants (48.7(9.1) to 49.3(9.2)). There were no significant differences between-groups for trunk support, Functional Ambulatory Categories, sensory exam (pin prick), scores, tone, bladder control questionnaire, bowel control, and AIS changes. 1 patient dropped out due to adverse reactions (acute disseminated encephalomyelitis)
Lima et al. 2010; Portugal Pre-post Level 4 N=20	Population: 17 males, 3 females; mean (SD) age 30.2(5.7); 15 patients AIS grade A, 5 patients AIS grad B; all > 1 YPI Treatment: OMA into the area of the SCI a mean of 49 months after injury, with pre-operative rehabilitation (mean (SD) 31.8(6.8) hours/week for 34.7(30) weeks) and post-operative rehabilitation (mean (SD) 32.7(5.2) hours/week for 92(37.6) weeks) with BIONT or robotic BWSTT. Outcome Measures: AIS score and AIS grade, FIM, WISCI	Estimated mean change in all ASIA neurological measures (pink prick, light touch, motor arms, motor legs) was statistically significant. ASIA motor legs score improved from 0 to 4.95(7.1) post intervention. 11 patients improved their AIS grades (6 by 2 grades), and 1 patient’s score deteriorated and suffered ARs (aseptic meningitis, spinal cord edema) 9 of the patients with an AIS score of 0 at baseline improved from 4 to 22 at last evaluation. Of the 13 patients assessed for functional studies, all had improvements on FIM scores (mean (SD) 71(23) to 85(28)) and WISCI scores (0.2(0.4) to 7.4(2.6)). Patients at facilities focusing on BIONT showed better motor recovery compared with those at facilities focusing on BWSTT. Voluntary motor potentials of the lower limb muscles were found in 11/20 patients.

Author Year; Country
Score
Research Design
ample Size

Methods

Outcomes

Kishk et al. 2010; Egypt
Case Control
Level 3
N=64

Population: Treated Group – 36 males, 7 females; mean (SD) age 31.7(10.4); 12 complete, 31 incomplete SCIControl Group – 15 males, 5 females; mean (SD) age 33.8(11.8); 3 complete, 17 incomplete SCI
Treatment: Monthly intrathecal injection of autologous bone marrow MSCs for 6 months, all participants received 3 rehabilitation therapies per week.
Outcome Measures: Trunk muscle assessment, MASS, Functional Ambulation Categories, AIS sensorimotor, motor and sensory scores, lower-limb somatosensory evoked potentials (SSEPS)

A significantly greater proportion of the treatment group showed improved motor scores, but this is not clinically relevant as it was only by 1-2 points in 18/44 participants (48.7(9.1) to 49.3(9.2)).
There were no significant differences between-groups for trunk support, Functional Ambulatory Categories, sensory exam (pin prick), scores, tone, bladder control questionnaire, bowel control, and AIS changes.
1 patient dropped out due to adverse reactions (acute disseminated encephalomyelitis)

Lima et al. 2010; Portugal
Pre-post
Level 4
N=20

Population: 17 males, 3 females; mean (SD) age 30.2(5.7); 15 patients AIS grade A, 5 patients AIS grad B; all > 1 YPI
Treatment: OMA into the area of the SCI a mean of 49 months after injury, with pre-operative rehabilitation (mean (SD) 31.8(6.8) hours/week for 34.7(30) weeks) and post-operative rehabilitation (mean (SD) 32.7(5.2) hours/week for 92(37.6) weeks) with BIONT or robotic BWSTT.
Outcome Measures: AIS score and AIS grade, FIM, WISCI

Estimated mean change in all ASIA neurological measures (pink prick, light touch, motor arms, motor legs) was statistically significant. ASIA motor legs score improved from 0 to 4.95(7.1) post intervention.
11 patients improved their AIS grades (6 by 2 grades), and 1 patient’s score deteriorated and suffered ARs (aseptic meningitis, spinal cord edema)
9 of the patients with an AIS score of 0 at baseline improved from 4 to 22 at last evaluation.
Of the 13 patients assessed for functional studies, all had improvements on FIM scores (mean (SD) 71(23) to 85(28)) and WISCI scores (0.2(0.4) to 7.4(2.6)).
Patients at facilities focusing on BIONT showed better motor recovery compared with those at facilities focusing on BWSTT.
Voluntary motor potentials of the lower limb muscles were found in 11/20 patients.

Discussion

One case control study investigated the effects of monthly intrathecal injections of MSCs in combination with 6 months of rehabilitation therapies on muscle strength and function (Kishk et al. 2010). There were no differences between groups for functional ambulation, but motor scores were slightly (but significantly) greater in the treatment group. Several patients experienced side effects, including increased spasticity, neuropathic pain, excessive sweating and transient hypertension. One patient withdrew from the study for severe adverse reactions to the treatment. Further studies are needed to establish safety, and controlled studies are needed to determine timing, dose, and duration of this intervention.

In a pre-post study, OMA were transplanted into the site of injury in persons with chronic complete or motor-complete SCI (Lima et al. 2010). Patients then underwent locomotor training (either robotic-assisted treadmill training or assisted overground walking training). Functional Independence Measure and Walking Index for Spinal Cord Injury scores improved in 13 participants tested, and this improvement correlated with increases in leg strength. Five of twenty patients experienced adverse events, where one patient developed aseptic meningitis and another developed irritable bowel syndrome. Other adverse events were easily treated or resolved on their own. Randomized controlled trials are necessary to further show the efficacy of this treatment.

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