**Bone Marrow–Derived Cells Regenerate Structural and Functional Lower Urinary Tracts**

Tetsuya Imamura, Osamu Ishizuka and Osamu Nishizawa

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/55558

## **1. Introduction**

In this chapter, we show that with the application of tissue engineering principles, utilization of bonemarrow-derivedcellshasthepotentialtoreconstructfunctionallowerurinarytracts,which are composed mainly of the urinary bladder [1] and urethra [2]. Patients complain about lower urinary tract dysfunctions that significantly decrease their quality of life. Regenerative medi‐ cine provides great hope for the recovery of lost tissue and organ functions. In urology, novel regenerativemedicinetechniquesarebeingdevelopedforthetreatmentofirreversiblydamaged lower urinary tracts. Notably, injection of autologous cells harvested from adipose tissue into the sphincter and urethra has been attempted clinically to treat urinary incontinence by increasing the urethral closure pressure [3]. Our laboratory has also been vigorously investigat‐ ing regenerativemedicine as a toolto treatirreversiblydamagedurinary bladders andurethras.

An important factor in the development of regenerative medicine is selection of the proper source for the regenerative cells and/or tissues. Recently, attempts to use various kinds of cells, such as induced pluripotent stem cells, embryonic stem cells, and mesenchymal cells derived from adipose and oral mucosal tissues, have been reported. Based on the literature, we have considered many sources of cells from which to derive adult somatic stem cells that could regenerate lower urinary tracts [4-7]. Recently, we have focused on two sources of cells with the potential to meet a variety of demands: bone marrow-derived cells [8] and adipose-derived cells [9]. In this chapter, we show that cells derived from bone marrow are an excellent resource for the development of regenerative medicine. These cells are capable of differentiating both in vitro and in vivo along multiple pathways that include striated and smooth muscle [10-16] as well as bone, cartilage, adipose, neural cells, tendon, and connective tissue [17,18]. Also, bone marrow-derived cells, which are easy to grow in culture, produce cytokines and growth

© 2013 Imamura et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

factors that accelerate healing in damaged tissues and inhibit apoptosis and the development of fibrosis [19,20]. However, the operation to harvest the bone marrow cells is generally considered to have higher patient risks compared to harvesting adipose cells. The increased risk for harvesting bone marrow cells for autologous transplantation is especially important for elderly patients with lower urinary tract symptoms (LUTS) and who may have other diseases as well.

Equally important as the sources of cells for regenerative medicine are the survival rates for implanted cells, the differentiation into target cell types, and the structural support that enables the reconstruction within the recipient tissues [21]. The survival, differentiation, and reorgan‐ ization of the implanted cells are affected by the microenvironment within the recipient tissues. However, our understanding of these microenvironments is currently insufficient to provide clinically effective and reliable resources for regenerative medicine. Thus, to obtain the optimum microenvironment, we need to investigate the utilization of scaffolds, growth factors, and combinations of these materials.

This chapter has three major topics: (1) implantation of allogenic mouse bone marrow-derived cells into freeze-injured urinary bladders, (2) implantation of autologous bone marrowderived cells into freeze-injured urethral sphincters, and (3) importance of the microenviron‐ ment in reconstructing functional lower urinary tracts. We show that bone marrow-derived cells implanted into freeze-injured bladders or urethras differentiate into smooth muscle and striated muscle cells. These cells become organized into layered structures that are associated with the recovery of tissue function. In injured tissues, we have begun to uncover the important roles that may support the differentiation. Our information leading to future studies will enable the development of regenerative medicine in urology and other clinical areas.
