Bilateral transplantation of allogenic adult human bone marrow-derived mesenchymal stem cells into the subventricular zone of Parkinson's disease: a pilot clinical study

Abstract

The progress of PD and its related disorders cannot be prevented with the medications available. In this study, we recruited 8 PD and 4 PD plus patients between 5 to 15 years after diagnosis. All patients received BM-MSCs bilaterally into the SVZ and were followed up for 12 months. PD patients after therapy reported a mean improvement of 17.92% during "on" and 31.21% during "off" period on the UPDRS scoring system. None of the patients increased their medication during the follow-up period. Subjectively, the patients reported clarity in speech, reduction in tremors, rigidity, and freezing attacks. The results correlated with the duration of the disease. Those patients transplanted in the early stages of the disease (less than 5 years) showed more improvement and no further disease progression than the later stages (11-15 years). However, the PD plus patients did not show any change in their clinical status after stem cell transplantation. This study demonstrates the safety of adult allogenic human BM-MSCs transplanted into the SVZ of the brain and its efficacy in early-stage PD patients.

Figure 1

Characterization of adult BM-MSCs prior to transplantation as per ISCT criteria. It shows the plastic adhered spindle-shaped fibroblast like appearance of adult BM-MSCs in culture (lower left panel). And the surface expression of CD markers (top panel: negative markers and lower panel: positive markers).

Figure 2

Shows the mean ± SD of the UPDRS score of the PD patients during “OFF” and “ON” periods at baseline and after stem cell transplantation. The scores have been assessed during the screening visit and final visit 12 months after transplantation. *Represents the level of significance.

Figure 3

Illustrates the improvement in UPDRS scores for PD patients before and after stem cell transplantation. The graph highlights the fact that the patients treated early at the onset of the disease (5 years) have shown significantly better improvement which correlates clinically. The patients that were treated between 10–15 years after the diagnosis of PD did not show any significant improvement.

Figure 4

Shows T2 FLAIR axial images. (a) Depicts bilateral asymmetric multifocal hyperintensities involving pontine base periventricular and deep white matter suggestive of small-vessel ischemia. Diffuse brain atrophy is also seen with mineralization below globus pallidus and substantia nigra indicative of PD. There is no significant difference noted between the baseline and follow-up MRI. (b) Depicts moderate brain atrophy with bilateral putaminal rim sign seen. Small-vessel ischemic changes are seen in the bilateral periventricular and deep white matter. Mineralization of bilateral lentiform nuclei, dentate nuclei, and substantia nigra visualized is suggestive of MSA-P or PD plus syndrome. There was no significant difference noted between the baseline and follow-up MRI.

Figure 5

Depicts the balance between degeneration due to illness and the neuroregenerative reserve present in the brain. The schematic diagram illustrates that higher the degeneration higher the illness and more the regeneration required. Exogenous supply of stem cells midway between these two stages (i.e., 50%) would aid in improving the quality of life and reducing the disability due to disease.