Induction of Smooth Muscle Cell-Like Phenotype in Marrow-Derived Cells among Regenerating Urinary Bladder Smooth Muscle Cells

Abstract

Tissue regeneration on acellular matrix grafts has great potential for therapeutic organ reconstruction. However, hollow organs such as the bladder require smooth muscle cell regeneration, the mechanisms of which are not well defined. We investigated the mechanisms by which bone marrow cells participate in smooth muscle formation during urinary bladder regeneration, using in vivo and in vitro model systems. In vivo bone marrow cells expressing green fluorescent protein were transplanted into lethally irradiated rats. Eight weeks following transplantation, bladder domes of the rats were replaced with bladder acellular matrix grafts. Two weeks after operation transplanted marrow cells repopulated the graft, as evidenced by detection of fluorescent staining. By 12 weeks they reconstituted the smooth muscle layer, with native smooth muscle cells (SMC) infiltrating the graft. In vitro, the differential effects of distinct growth factor environments created by either bladder urothelial cells or bladder SMC on phenotypic changes of marrow cells were examined. First, supernatants of cultured bladder cells were used as conditioned media for marrow cells. Second, these conditions were reconstituted with exogenous growth factors. In each case, a growth factor milieu characteristic of SMC induced an SMC-like phenotype in marrow cells, whereas that of urothelial cells failed. These findings suggest that marrow cells differentiate into smooth muscle on acellular matrix grafts in response to the environment created by SMC.

Use of a latex biomembrane for bladder augmentation in a rabbit model: biocompatibility, clinical and histological outcomes

“…Some authors suggest a major role for pluripotential stem cells in the graft cellular regeneration (19,20). On the other hand, other authors have demonstrated that muscle layer regeneration occurs by migration of dedifferentiated bladder SMC from the matrixbladder junction (15).…”

A Nonhuman Primate Model for Urinary Bladder Regeneration Using Autologous Sources of Bone Marrow-Derived Mesenchymal Stem Cells

“…Experimental data has demonstrated the utility of bone marrow (BM) cells in a bladder regenerative setting with data suggesting the phenotypic and physiological similarities between mesenchymal stem cells (MSCs) and bSMCs [7][8][9]. The characterization of a battery of contractile proteins shows that MSCs have a contractile protein profile similar to bSMCs [8].…”

Updates on stem cells and their applications in regenerative medicine

“…Bladder tissue engineering using MSCs might show better results than by using differentiated cells. MSCs were shown to migrate to the bladder grafts and differentiate into smooth muscle cells (Kanematsu et al, 2005). These cells achieved fast repopulation of the grafts, which exhibited appropriate neural function and less fibrosis (Chung et al, 2005 (Zhang et al, 2005), and thus the use of MSCs may help to engineer a bladder when no bladder-derived cells are available.…”