Name of journal: World Journal of Transplantation esps manuscript no: 18452 Manuscript Type: Original Article Retrospective Study

Evaluation of bladder repair in SCI patients after HSCs and HPs transplantation

Efficacy of the rapier of bladder functions was evaluated in 72 patients with the assessment of neurologic condition that included 3-point assessment of the feeling of urination and 5-point assessment of urine retention. Total score that denotes absence of neurologic signs of urinary disorder is 8 points.

Repair of the urinary system was observed in 47.7% of the cases after the intrathecal transplantation of HSCs and HPs. Clinically, the restoration of urinary system manifested in creeping sensation in the body or unpleasant feelings in the lower abdomen that preceded involuntary urination, but complete syndrome of vegetative hyperreflexia was absent (changes in blood pressure and heart rate, arrhythmia, sweating, fever above the injury level). Many patients observed the feeling of weak “swelling” above pubic symphysis that allowed beginning of bladder training with closing urethral or cystostomic catheter. Further restoration of the capacity to retain urine for at least 1-3 min led to intermittent catheterization, or refusal from the cystostomy. In some cases, 3-5 intrathecal transplantations of HSCs and HPs resulted in full refusal from intermittent catheterizations and further complete repair of urinary function.

Analysis of the clinical data showed that in 33.8% cases the manifestations of urinary restoration began after the first transplantation of HSCs and HPs, showing clinical improvement from baseline 0.4 ± 0.2 points to 1.2 ± 0.2 points after the first transplantation of HSCs and HPs (P < 0.05) (Figure 12). Consequent transplantations improved the urinary function further, thus increasing the score to 1.9 ± 0.4 points.

Hence, the transplantation of HSCs and HPs can lead to gradual restoration of urinary function in chronic SCI cases. Analysis of the data, depending on the level of injury (Figure 13), showed that largely, the improvement in the urinary system after HSCs and HPs transplantation was noted at Th3-Th8 level of SCI and at the level of lumbar enlargement (70%). It manifested in the increasing urinary restoration (Figure 13) from baseline 1.1 ± 0.8 points to 2.5 ± 0.8 points after the first transplantation and to 2.9 ± 0.9 points after the repeated HSCs and HPs transplantations (P < 0.05 between the therapy stages) in Th3-Th8 SCI cases. In SCI at the level of lumbar enlargement the urinary function changed from baseline 1 point to 1.9 and 2.8 after the first and the second transplantations, respectively (P < 0.05 between the therapy stages).

Despite fewer number of the SCI patients at the level of cervical intumescence, who showed the urinary system repair (36.8%), the restoration from baseline 0.1 points to 0.7 points and to 1.3 points was clinically registered after the first HSCs and HPs transplantation after the second HSCs and HPs transplantation, respectively (P < 0.05 between the therapy stages).

Thus, the urinary system after the intrathecal transplantation of the HSCs and HPs restores irrespective of the level of the spinal cord injury. However, the urinary system restores more efficiently in the cases of SCI at the level of Th3-Th8 and lumbar enlargement.

The repair of the urinary system after HSCs and HPs transplantation did not depend on the type of SCI, as shown in Figure 14A. However, in the cases of the incomplete SCI the urinary disorder at a baseline was less significant, as well as after the first transplantation. After the second transplantation, no statistically significant changes in the clinical evaluation of urinary system have been observed.

Restoration of the urinary system did not depend on period post injury, either. As seen in Figure 14B, some restoration of urinary function was observed irrespectively from years post injury. There is a clear tendency for further improvement of urinary function after 2 or 3 years of HSCs and HPs therapy, as compared to baseline.

Consequently, the intrathecal transplantation of HSCs and HPs in chronic SCI patients is an efficient method to repair urinary function. The lower levels of SCI are more prone to restore urinary function, which can be explained by closer location of urination centers in sacral spinal segments to lesion sites and, possibly, by larger concentration of HSCs and HPSs in the sites of injury. Herewith, neither the type of injury, nor years post injury, do not influence restoration of urinary function.