Potential differentiation of human mesenchymal stem cell transplanted in rat corpus cavernosum toward endothelial or smooth muscle cells

Abstract

One of the causes of erectile dysfunction (ED) is the damaged penile cavernous smooth muscle cells (SMCs) and sinus endothelial cells (ECs). To investigate the feasibility of applying immortalized human mesenchymal stem cells (MSCs) to penile cavernous ECs or SMCs repair in the treatment of ED, the in vivo potential differentiation of the immortalized human MSCs toward penile cavernous endothelial or smooth muscle was investigated. One clone of immortalized human bone marrow mesenchymal stem cell line B10 cells via retroviral vector encoding v-myc were transplanted into the cavernosum of the Sprague-Dawley rats and harvested 2 weeks later. The expression of CD31, von Willebrand factor (vWF), smooth muscle cell actin (SMA), calponin and desmin was determined immunohistochemically in rat penile cavernosum. Multipotency of B10 to adipogenic, osteogenic or chondrogenic differentiation was found. Expression of EC specific markers (CD31 or vWF protein) and expression of SMC specific markers (calponin, SMA or desmin protein) were demonstrated in grafted B10 cells. When human MSCs were transplanted into the penile cavernosum, they have the potential to differentiate toward ECs or SMCs. Human MSCs may be a good candidate in the treatment of penile cavernosum injury.

Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer

“…32 MSC might even contribute to tumor angiogenesis, although this latter point is critically discussed. 33,34 While the molecular processes that drive migration of MSC to tumor tissues remain unclear, the tropism of MSC to tumor tissues is suggested to be mediated, at least in part, by specific growth factors and chemokines, 30,31 such as also shown in the present study on PDGF. Consequently, to inhibit the growth of tumors in situ by MSC, genetic modification of MSC is necessary to produce high levels of anticancer agents that blunt tumor growth kinetics.…”

Effect of muscle‐derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat

“…Although there was an improvement in erectile function and neurofilament staining even at 3 months after injection of the stem cells, no surviving stem cells were found nor were any SMC markers investigated, as the primary objective of that study was to achieve nerve regeneration. A more recent report did claim that implantation of human bone marrow mesenchymal stem cells into the normal rat corpora resulted at 2 weeks in the differentiation of these stem cells into both endothelial and SMCs, but retrovirusimmortalized cells and not truly selfreplicating cells were used [21]. A more convincing study was performed with native rat bone marrow mesenchymal stem cells engineered to express endothelial nitric oxide synthase, where these stem cells were injected into the corpora cavernosa of aged rats [22].…”

“…To date, only a few studies of stem cell implantation in experimental models of ED, to repair either nerves or smooth muscle in the corpora, have been conducted [20][21][22][23], although stem cells are also being investigated for the repair of other urogenital organs, such as the bladder, urethra, and kidney [24][25][26][27]. The first study in the penis [20] was based on the injection of rat embryonic stem cells modified ex vivo to express brain-derived nerve growth factor into the corpora cavernosa in a rat model of cavernosal nerve damage.…”

ROS activates JNK-mediated autophagy to counteract apoptosis in mouse mesenchymal stem cells in vitro

“…Disappointing effects in diabetes patients compared with the general population have been reported [5][6][7] . Because stem cells can directionally differentiate into corpus cavernosum vascular endothelial cells and smooth muscle cells under a specific microenvironment, the transplantation of stem cells for treating diabetic ED was proposed as a potential therapeutic approach [8][9][10] . Mesenchymal stem cells (MSCs) have been tested in transplantation therapy for diabetic ED [11][12][13] .…”