The Microenvironment of Freeze-Injured Mouse Urinary Bladders Enables Successful Tissue Engineering

Imamura, Tetsuo; Yamamoto, Takatsugu; Ishizuka, Osamu; Gotoh, Momokazu; Nishizawa, Osamu

doi:10.1089/ten.tea.2009.0038

Cited by 18 publications

(49 citation statements)

References 45 publications

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“…To achieve clinically significant regeneration with these cells, it may be necessary to combine them with tissue engineering techniques that utilize scaffolds and/or growth factors. 43 In any case, our study clearly showed that in rabbits the injection of bone-marrow-derived cells accelerated the recovery of urinary sphincters compared to cell-free injections.…”

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confidence: 49%

“…We believe that the distinct presence of myoblast-like cells at 14 days suggests that recovery of the muscle tissues might have stopped further development of the GFP-Pax7 double-positive myoblasts into striated or smooth muscle cells. 43 Understanding the controls for differentiation of the implanted cells is very important for the further development of regenerative medicine. While we do not understand the regulatory controls that govern the differentiation of the urethral striated and smooth muscle cells, it is clear that the presence of the myoblasts in the regenerated region may have important long-term significance.…”

mentioning

confidence: 99%

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Implantation of Autologous Bone-Marrow-Derived Cells Reconstructs Functional Urethral Sphincters in Rabbits

Imamura

Ishizuka

Kinebuchi

et al. 2011

Tissue Engineering Part A

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The purpose of this study was to determine if implantation of autologous bone-marrow-derived cells has the potential to treat stress urinary incontinence caused by intrinsic sphincter deficiency. Bone marrow cells harvested from femurs of New Zealand White rabbits were cultured for 10 days. Seven days before implantation, the urethral sphincters located at the internal urethral orifice were cryo-injured by spraying liquid nitrogen for 15 s. The cultured autologous bone-marrow-derived cells were implanted 7 days after cryo-injury. For controls, cell-free solutions were injected. At 7 and 14 days after implantation, leak point pressures were determined and the urethral sphincters were examined by immunohistochemistry. At 7 and 14 days, the cell-implanted regions contained numerous striated and smooth muscle-like cells expressing myoglobin and smooth muscle actin, respectively. The proportions of myoglobin-and smooth muscle actin-expressing areas in both the 7-and 14-day cell-implanted regions were significantly higher than in controls. By 14 days, these differentiated cells formed contacts with similar cells, creating layered muscle structures. At that time, the leak point pressure of the cellimplanted rabbits was significantly higher than that of the controls. In conclusion, autologous bone-marrowderived cells can reconstruct functional urethral sphincters.

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confidence: 49%

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confidence: 99%

Implantation of Autologous Bone-Marrow-Derived Cells Reconstructs Functional Urethral Sphincters in Rabbits

Imamura

Ishizuka

Kinebuchi

et al. 2011

Tissue Engineering Part A

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“…43 We do not yet know whether the urinary bladders that are damaged due to clinical radiotherapy have a suitable microenvironment for bone marrow-derived cell growth and differentiation. A further clinical complication is that radiotherapy often induces more serious damage, including loss of bladder tissues, bladder shrinkage with fibrosis, and synechia between urinary bladders and intestines.…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow-Derived Cells Implanted into Radiation-Injured Urinary Bladders Reconstruct Functional Bladder Tissues in Rats

Imamura

Ishizuka

Zhang

et al. 2012

Tissue Engineering Part A

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The purpose of this study was to determine whether bone marrow-derived cells implanted into radiation-injured urinary bladders could reconstruct functional bladder tissues. The pelvic region of anesthetized female SpragueDawley (SD) rats was irradiated with 2 Gy once a week for 5 weeks. After the last irradiation, the rats were maintained for 2 weeks. Bone marrow cells were harvested from the femurs of donor male green fluorescence protein (GFP)-transfected SD rats and cultured for 7 days. Two weeks after the last radiation exposure, the cultured adherent, proliferating bone marrow-derived cells were implanted into the walls of irradiated urinary bladders. For controls, cell-free solutions were similarly injected. Four weeks after donor cell or control implantations, cystometric, histological, and immunohistochemical investigations were performed. Two weeks after the last irradiation, the smooth muscle layers and nerve fibers of the irradiated urinary bladders were disorganized. The proportions of smooth muscle layer and nerve fiber areas were significantly decreased compared with sham-irradiated urinary bladders. In addition, the remaining smooth muscle cells within the irradiated urinary bladders expressed P4HB, an indicator of collagen synthesis. In the cystometric investigations, the voiding interval of irradiated rats was irregularly prolonged, 7.92 -1.09 min, and the residual volume, 0.13 -0.03 mL, was significantly higher compared with the sham-irradiated rats (5.50 -0.43 mL and 0.05 -0.01 mL). After 4 weeks, the smooth muscle layers and nerve fibers in the cell-free control urinary bladders remained similar to the preimplanted irradiated urinary bladders; however, the cell-implanted urinary bladders contained reconstructed smooth muscle layers and nerve fibers, the proportions of each were significantly higher than those in the cell-free injected controls. The expression of P4HB within the cell-implanted urinary bladders decreased. Some GFPpositive implanted cells differentiated into smooth muscle-and nerve-like cells and became organized into the reconstructed tissues. The voiding interval of the cell-implanted rats, 5.46 -0.33 min, was regular and similar to that of the sham-irradiated rats, and significantly less than that of the cell-free injected controls, 7.39 -0.54 min. The residual volume, 0.04 -0.01 mL, was similar to that of the sham-irradiated rats and significantly decreased compared with that of the cell-free injected controls, 0.15 -0.05 mL. Therefore, the implantation of bone marrowderived cells is a potentially useful treatment for radiotherapy-induced urinary dysfunctions.

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“…Imamura et al . have reported that bone marrow derived MSC differentiated into smooth muscles in the rat urinary bladder 14,15 . More recently, Lin et al .…”

Section: Introductionmentioning

confidence: 97%

Increased urethral resistance by periurethral injection of low serum cultured adipose‐derived mesenchymal stromal cells in rats

Watanabe¹,

Maruyama²,

Yamamoto

et al. 2011

Int J of Urology

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Objectives:To evaluate the effects of a periurethral injection of low serum cultured adipose tissue-derived mesenchymal stromal cells (LASC) and to develop a new autologous cell therapy for stress urinary incontinence. Methods: F344 rats were divided into three groups as based on the periurethral injection of LASC, GAX collagen or vehicle (control). At 2 and 4 weeks after injection, leak point pressure (LPP) was measured before and after transection of the pelvic nerves. For cell tracking, LASC of green fluorescent protein transgenic rats were injected into nude rats. Results: At 2 weeks, both the LASC and collagen groups showed significantly higher LPP than the control group. At 4 weeks, the increase in LPP in the LASC group remained , whereas LPP in the collagen group decreased to baseline levels. In the absence of the urethral closure reflex after transection of the pelvic nerves, LPP in the LASC group was significantly higher than that in the other two groups. Histologically, the size of the urethral lumen was smaller in the LASC group than the collagen group. At 4 weeks, most of the LASC were positive for myogenic antigens including a-smooth muscle actin, desmin and calponin I. Conclusions: Periurethral injection of autologous LASC capable of myogenic differentiation made a greater contribution to the increase in urethral resistance than did the conventional collagen bulk injection. Thus, its use for treatment of stress urinary incontinence can be postulated.

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The Microenvironment of Freeze-Injured Mouse Urinary Bladders Enables Successful Tissue Engineering

Cited by 18 publications

References 45 publications

Implantation of Autologous Bone-Marrow-Derived Cells Reconstructs Functional Urethral Sphincters in Rabbits

Implantation of Autologous Bone-Marrow-Derived Cells Reconstructs Functional Urethral Sphincters in Rabbits

Bone Marrow-Derived Cells Implanted into Radiation-Injured Urinary Bladders Reconstruct Functional Bladder Tissues in Rats

Increased urethral resistance by periurethral injection of low serum cultured adipose‐derived mesenchymal stromal cells in rats

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