Continuous Improvement after Multiple Mesenchymal Stem Cell Transplantations in a Patient with Complete Spinal Cord Injury

Abstract

Interruption of spinal cord (SC) continuity leads to functional loss below the lesion level. The purpose of this study was to evaluate the safety and efficacy of bone marrow nucleated cell (BMNC) and multiple mesenchymal stem cell (MSC) transplantations in spinal cord injury (SCI). A patient with total SC interruption at the Th2-3 level underwent experimental therapy with BMNC and MSC transplantations followed with intensive neurorehabilitation treatment. At admission, 6 h after SCI, the patient was scored ASIA A, had a Th1 sensation level, paraplegia with sphincter palsy, and was without the ability to control trunk movement. Neurophysiology examination showed bilateral axonal damage to the motor and sensory neural fibers with no motor unit potentials or peripheral motor nerve conduction in the lower extremities. The standard therapy had been applied and had not produced any positive results. The patient was treated with autologous BMNCs injected intravenously (3.2 × 10 9 ) and intrathecally (0.5 × 10 9 ) 10 weeks after the SCI and with five rounds of MSCs every 3-4 months (1.3-3.65 × 10 7 ) administered via lumbar puncture. Total number of transplanted MSC cells during the course of treatment was 1.54 × 10 8 . There were no complications related to transplantations and no side effects related to the therapy during 2 years of treatment. The ASIA score improved from A to C/D (from 112 to 231 points). The sensation level expanded from Th1 to L3-4, and the patient's ability to control the body trunk was fully restored. Bladder filling sensation, bladder control, and anal sensation were also restored. Muscle strength in the left lower extremities improved from plegia to deep paresis (1 on the Lovett scale). The patient's ability to move lower extremities against gravity supported by the movements in quadriceps was restored. The patient gained the ability to stand in a standing frame and was able to walk with the support of hip and knee ortheses. Magnetic resonance imaging (MRI) revealed that at the Th2/Th3 level, where the hemorrhagic necrosis was initially observed, small tissue structures appeared. Our results suggest that repeated intrathecal infusions of MSCs might have the potential to produce clinically meaningful improvements for SCI patients.

Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation

“…These results collectively suggest it is plausible that direct axonal connections from motor cortex neurons to spinal cord are not essential for reestablishment of basic locomotion after mammalian SCI (55)(56)(57). Our results help define recovery neurobiology: the lesioned adult CNS may use neural circuits not identical to those deployed under normal physiological conditions for functional improvement.…”

Lineage Commitment, Signaling Pathways, and the Cytoskeleton Systems in Mesenchymal Stem Cells

“…8 hMCSs are now used in clinical trials as a therapeutic resource against a variety of immune-related and age-related diseases, including neurodegenerative, osteoporosis, cardiovascular, and some others. [9][10][11] The following elements of MSC biology will be discussed in the current review: (1) interaction of MSCs with the extracellular matrix (ECM) and mechanotransduction; (2) morphological and cytoskeleton changes of MSCs during differentiation; and (3) major signaling pathways involved in the differentiation of MSCs.…”

Zastosowanie wielokrotnych podań mezenchymalnych komórek macierzystych pochodzących z galarety Whartona w leczeniu niepełnego uszkodzenia rdzenia kręgowego – opis przypadku

“…Co ciekawe, opublikowane doniesienia wykazały najlepsze postępy w leczeniu pacjentów z uszkodzeniem rdzenia kręgowego, u których wykonano intensywną rehabilitację/neurorehabilitację w połączeniu z terapią komórkową. Ponadto większość sprawozdań wykorzystuje strategię implantacji mnogiej [21,23,25,29,30,31]. Dostępne dane wydają się więc wskazywać na przydatność metody wielokrotnego wszczepiania WJMSC w połączeniu z intensywną rehabilitacją/neurorehabilitacją w celu maksymalizacji skuteczności terapii komórkowej u pacjentów z urazami rdzenia kręgowego.…”