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Intraurethral co-transplantation of bone marrow mesenchymal stem cells and muscle-derived cells improves the urethral closure

Burdzinska, Anna; Dybowski, Bartosz; Zarychta-Wiśniewska, Weronika; Kulesza, Agnieszka; Butrym, Marta LU ; Zagozdzon, Radoslaw; Graczyk-Jarzynka, Agnieszka; Radziszewski, Piotr; Gajewski, Zdzislaw and Paczek, Leszek (2018) In Stem Cell Research and Therapy 9(1).
Abstract

Background: Cell therapy constitutes an attractive alternative to treat stress urinary incontinence. Although promising results have been demonstrated in this field, the procedure requires further optimization. The most commonly proposed cell types for intraurethral injections are muscle derived cells (MDCs) and mesenchymal stem/stromal cell (MSCs). The aim of this study was to evaluate the effects of MDC-MSC co-transplantation into the urethra. Methods: Autologous transplantation of labeled MDCs, bone marrow MSCs or co-transplantation of MDC-MSC were performed in aged multiparous female goats (n = 6 in each group). The mean number of cells injected per animal was 29.6 × 106(± 4.3 × 106). PBS-injected animals... (More)

Background: Cell therapy constitutes an attractive alternative to treat stress urinary incontinence. Although promising results have been demonstrated in this field, the procedure requires further optimization. The most commonly proposed cell types for intraurethral injections are muscle derived cells (MDCs) and mesenchymal stem/stromal cell (MSCs). The aim of this study was to evaluate the effects of MDC-MSC co-transplantation into the urethra. Methods: Autologous transplantation of labeled MDCs, bone marrow MSCs or co-transplantation of MDC-MSC were performed in aged multiparous female goats (n = 6 in each group). The mean number of cells injected per animal was 29.6 × 106(± 4.3 × 106). PBS-injected animals constituted the control group (n = 5). Each animal underwent urethral pressure profile (UPP) measurements before and after the injection procedure. The maximal urethral closure pressure (MUCP) and functional area (FA) of UPPs were calculated. The urethras were collected at the 28th or the 84th day after transplantation. The marker fluorochrome (DID) was visualized and quantified using in vivo imaging system in whole explants. Myogenic differentiation of the graft was immunohistochemically evaluated. Results: The grafted cells were identified in all urethras collected at day 28 regardless of injected cell type. At this time point the strongest DID-derived signal (normalized to the number of injected cells) was noted in the co-transplanted group. There was a distinct decline in signal intensity between day 28 and day 84 in all types of transplantation. Both MSCs and MDCs contributed to striated muscle formation if transplanted directly to the external urethral sphincter. In the MSC group those events were rare. If cells were injected into the submucosal region they remained undifferentiated usually packed in clearly distinguishable depots. The mean increase in MUCP after transplantation in comparison to the pre-transplantation state in the MDC, MSC and MDC-MSC groups was 12.3% (± 11.2%, not significant (ns)), 8.2% (± 9.6%, ns) and 24.1% (± 3.1%, p = 0.02), respectively. The mean increase in FA after transplantation in the MDC, MSC and MDC-MSC groups amounted to 17.8% (± 15.4%, ns), 15.2% (± 12.9%, ns) and 17.8% (± 2.5%, p = 0.04), respectively. Conclusions: The results suggest that MDC-MSC co-transplantation provides a greater chance of improvement in urethral closure than transplantation of each population alone.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Autologous transplantation, Cell transplantation, Co-transplantation, Mesenchymal stem cells, Muscle-derived cells, Urinary incontinence
in
Stem Cell Research and Therapy
volume
9
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85053848603
ISSN
1757-6512
DOI
10.1186/s13287-018-0990-2
language
English
LU publication?
yes
id
c08357f8-d688-4737-84d6-a587c26a1197
date added to LUP
2018-10-11 07:12:04
date last changed
2019-02-20 11:31:00
@article{c08357f8-d688-4737-84d6-a587c26a1197,
  abstract     = {<p>Background: Cell therapy constitutes an attractive alternative to treat stress urinary incontinence. Although promising results have been demonstrated in this field, the procedure requires further optimization. The most commonly proposed cell types for intraurethral injections are muscle derived cells (MDCs) and mesenchymal stem/stromal cell (MSCs). The aim of this study was to evaluate the effects of MDC-MSC co-transplantation into the urethra. Methods: Autologous transplantation of labeled MDCs, bone marrow MSCs or co-transplantation of MDC-MSC were performed in aged multiparous female goats (n = 6 in each group). The mean number of cells injected per animal was 29.6 × 10<sup>6</sup>(± 4.3 × 10<sup>6</sup>). PBS-injected animals constituted the control group (n = 5). Each animal underwent urethral pressure profile (UPP) measurements before and after the injection procedure. The maximal urethral closure pressure (MUCP) and functional area (FA) of UPPs were calculated. The urethras were collected at the 28th or the 84th day after transplantation. The marker fluorochrome (DID) was visualized and quantified using in vivo imaging system in whole explants. Myogenic differentiation of the graft was immunohistochemically evaluated. Results: The grafted cells were identified in all urethras collected at day 28 regardless of injected cell type. At this time point the strongest DID-derived signal (normalized to the number of injected cells) was noted in the co-transplanted group. There was a distinct decline in signal intensity between day 28 and day 84 in all types of transplantation. Both MSCs and MDCs contributed to striated muscle formation if transplanted directly to the external urethral sphincter. In the MSC group those events were rare. If cells were injected into the submucosal region they remained undifferentiated usually packed in clearly distinguishable depots. The mean increase in MUCP after transplantation in comparison to the pre-transplantation state in the MDC, MSC and MDC-MSC groups was 12.3% (± 11.2%, not significant (ns)), 8.2% (± 9.6%, ns) and 24.1% (± 3.1%, p = 0.02), respectively. The mean increase in FA after transplantation in the MDC, MSC and MDC-MSC groups amounted to 17.8% (± 15.4%, ns), 15.2% (± 12.9%, ns) and 17.8% (± 2.5%, p = 0.04), respectively. Conclusions: The results suggest that MDC-MSC co-transplantation provides a greater chance of improvement in urethral closure than transplantation of each population alone.</p>},
  articleno    = {239},
  author       = {Burdzinska, Anna and Dybowski, Bartosz and Zarychta-Wiśniewska, Weronika and Kulesza, Agnieszka and Butrym, Marta and Zagozdzon, Radoslaw and Graczyk-Jarzynka, Agnieszka and Radziszewski, Piotr and Gajewski, Zdzislaw and Paczek, Leszek},
  issn         = {1757-6512},
  keyword      = {Autologous transplantation,Cell transplantation,Co-transplantation,Mesenchymal stem cells,Muscle-derived cells,Urinary incontinence},
  language     = {eng},
  month        = {09},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Stem Cell Research and Therapy},
  title        = {Intraurethral co-transplantation of bone marrow mesenchymal stem cells and muscle-derived cells improves the urethral closure},
  url          = {http://dx.doi.org/10.1186/s13287-018-0990-2},
  volume       = {9},
  year         = {2018},
}