madman
Super Moderator
Abstract
The majority of current treatment strategies against erectile dysfunction (ED) have consisted of only supportive care to sustain enough erection during sexual intercourse. In this study, we investigated whether the cultured conditioned medium of human exfoliated deciduous dental pulp stem cells (SHED-CM) had the ability to treat ED through fundamentally repairing the pathological damage of vascular endothelial cells of the corpus cavernosum. An open-label pilot study was performed from April 2016 to October 2020. SHED-CM was injected directly into the corpus cavernosum of the penis of 38 ED patients who visited our clinic and fulfilled the inclusion criteria. Efficacy was assessed using the simplified International Index of Erectile Function (IIEF-5) questionnaire. The average age and initial IIEF-5 score of the patients enrolled in this study was 56 (31–79) years old and 13.1 (5–20) points, respectively. Medical history revealed 7 patients with diabetes, 7 patients with hypertension, and 1 patient with priapism undergone shunt operation. Of these, 37 patients (97.4%) showed an improvement in IIEF-5 of an average of 19.3 (7–25) points or 64.4 (10–300) % increase after three injections of SHED-CM. Eighteen patients (47.4%) achieved more than 21 points (no ED) in IIEF-5. No adverse events were encountered. This is the first clinical report of ED treatment in the literature evaluating the efficacy of SHED-CM. Treatment with SHED-CM is expected to repair vascular damages of the corpus cavernosum, which are the main cause of ED, and to be widely spread as a fundamental clinical application for ED.
1 | INTRODUCTION
Erectile dysfunction (ED) is widely known to increase with aging.1 It has been estimated that 1 in 3 Japanese men over 40 years old has ED due to the diversification of lifestyle-related diseases and the increase in social stress.2 Thus, the number of ED patients in Japan has been estimated to be 11.3 million.3 According to the research of Yafi FA, et al., more than 80% of the cause of ED has an organic etiology and, of them, the vasculogenic disorder is the most common and can involve arterial inflow disorders and abnormalities of venous outflow (corporeal veno-occlusion) of corpus cavernosum.4 Since 1998, a couple of phosphodiesterase type 5 inhibitors (PDE5I) have been available as oral medication of ED. However, novel therapies are long expected to be developed because of the risks of PDE5I including rare but serious adverse effects of myocardial infarction and the fact that these conventional treatments were only used as transient care to sustain enough erection during sexual intercourse. Recently, human umbilical cord blood stem cells have shown beneficial effects on the erectile function when administered into the penises of men with severe type 2 diabetes.5 However, this effect was short-lived and not durable. In the meantime, in basic research of the field of regenerative medicine worldwide, a number of papers have shown that bioactive substances secreted from stem cells in vitro are more important for tissue regeneration than stem cells themselves.6–9 We have recently conducted a clinical pilot study of regenerative medicine on androgenic alopecia using a stem cell-derived growth factor, which is produced from the components of conditioned media where stem cells derived from the exfoliated deciduous dental pulp (SHED-CM) during the transformation of deciduous teeth into permanent teeth is cultured (manuscript in submission). In this clinical study, with the aim of establishing preemptive self-regenerative medicine, we investigated whether the recovery of sexual function can be achieved through the cellular regeneration of damaged vascular tissue in the corpus cavernosum of the penis by direct SHED-CM injection.
4 | DISCUSSION
Research into regenerative medicine, in which stem cells including induced pluripotent stem (iPS) cells and embryonic stem (ES) cells are transplanted, is drawing attention as a new treatment for central nervous system diseases such as cerebral infarction and spinal cord injury.12,13 However, there are many problems with stem cell transplantation, such as hazardous immune rejection against allografts and potential oncogenetic risk as well as complicating the process of preservation and culture methods of iPS/ES cells.14–16 Recently, various studies have demonstrated that culture supernatants of stem cells possess the ability to repair damaged tissues, protect tissues, and ultimately regenerate organs by utilizing their own stem cells in situ. 17 As such, the use of culture supernatant of stem cells is expected to be a next-generation therapy in the field of regenerative medicine, which had been once thought to take a long time to translate into clinical application.
Our SHED-CM treatment is characterized by the use of stem cells from rapidly differentiating deciduous dental pulp tissue, all of which are formulated in our hospital bio laboratory under a GMP grade quality control. SHED-CM is a generic therapeutic agent that is generated directly from a conditioned medium, in which liquid components are produced by the culturing of stem cells. Originally, SHED-CM therapy was developed based on research by Ueda M, et al.18 CM was originally made from stem cells of bone marrow, fat and umbilical cord. Recently, it has been reported that the CM of stem cells from deciduous or permanent dental pulps contains a large number of proteins and cytokines.8,19
5 | CONCLUSION
This is the first clinical report of ED treatment in the literature with the use of SHED-CM. Treatment with SHED-CM is expected to repair vascular damages of the corpus cavernosum, which are the main cause of ED, and to be widely spread as a fundamental clinical application for ED patients.
The majority of current treatment strategies against erectile dysfunction (ED) have consisted of only supportive care to sustain enough erection during sexual intercourse. In this study, we investigated whether the cultured conditioned medium of human exfoliated deciduous dental pulp stem cells (SHED-CM) had the ability to treat ED through fundamentally repairing the pathological damage of vascular endothelial cells of the corpus cavernosum. An open-label pilot study was performed from April 2016 to October 2020. SHED-CM was injected directly into the corpus cavernosum of the penis of 38 ED patients who visited our clinic and fulfilled the inclusion criteria. Efficacy was assessed using the simplified International Index of Erectile Function (IIEF-5) questionnaire. The average age and initial IIEF-5 score of the patients enrolled in this study was 56 (31–79) years old and 13.1 (5–20) points, respectively. Medical history revealed 7 patients with diabetes, 7 patients with hypertension, and 1 patient with priapism undergone shunt operation. Of these, 37 patients (97.4%) showed an improvement in IIEF-5 of an average of 19.3 (7–25) points or 64.4 (10–300) % increase after three injections of SHED-CM. Eighteen patients (47.4%) achieved more than 21 points (no ED) in IIEF-5. No adverse events were encountered. This is the first clinical report of ED treatment in the literature evaluating the efficacy of SHED-CM. Treatment with SHED-CM is expected to repair vascular damages of the corpus cavernosum, which are the main cause of ED, and to be widely spread as a fundamental clinical application for ED.
1 | INTRODUCTION
Erectile dysfunction (ED) is widely known to increase with aging.1 It has been estimated that 1 in 3 Japanese men over 40 years old has ED due to the diversification of lifestyle-related diseases and the increase in social stress.2 Thus, the number of ED patients in Japan has been estimated to be 11.3 million.3 According to the research of Yafi FA, et al., more than 80% of the cause of ED has an organic etiology and, of them, the vasculogenic disorder is the most common and can involve arterial inflow disorders and abnormalities of venous outflow (corporeal veno-occlusion) of corpus cavernosum.4 Since 1998, a couple of phosphodiesterase type 5 inhibitors (PDE5I) have been available as oral medication of ED. However, novel therapies are long expected to be developed because of the risks of PDE5I including rare but serious adverse effects of myocardial infarction and the fact that these conventional treatments were only used as transient care to sustain enough erection during sexual intercourse. Recently, human umbilical cord blood stem cells have shown beneficial effects on the erectile function when administered into the penises of men with severe type 2 diabetes.5 However, this effect was short-lived and not durable. In the meantime, in basic research of the field of regenerative medicine worldwide, a number of papers have shown that bioactive substances secreted from stem cells in vitro are more important for tissue regeneration than stem cells themselves.6–9 We have recently conducted a clinical pilot study of regenerative medicine on androgenic alopecia using a stem cell-derived growth factor, which is produced from the components of conditioned media where stem cells derived from the exfoliated deciduous dental pulp (SHED-CM) during the transformation of deciduous teeth into permanent teeth is cultured (manuscript in submission). In this clinical study, with the aim of establishing preemptive self-regenerative medicine, we investigated whether the recovery of sexual function can be achieved through the cellular regeneration of damaged vascular tissue in the corpus cavernosum of the penis by direct SHED-CM injection.
4 | DISCUSSION
Research into regenerative medicine, in which stem cells including induced pluripotent stem (iPS) cells and embryonic stem (ES) cells are transplanted, is drawing attention as a new treatment for central nervous system diseases such as cerebral infarction and spinal cord injury.12,13 However, there are many problems with stem cell transplantation, such as hazardous immune rejection against allografts and potential oncogenetic risk as well as complicating the process of preservation and culture methods of iPS/ES cells.14–16 Recently, various studies have demonstrated that culture supernatants of stem cells possess the ability to repair damaged tissues, protect tissues, and ultimately regenerate organs by utilizing their own stem cells in situ. 17 As such, the use of culture supernatant of stem cells is expected to be a next-generation therapy in the field of regenerative medicine, which had been once thought to take a long time to translate into clinical application.
Our SHED-CM treatment is characterized by the use of stem cells from rapidly differentiating deciduous dental pulp tissue, all of which are formulated in our hospital bio laboratory under a GMP grade quality control. SHED-CM is a generic therapeutic agent that is generated directly from a conditioned medium, in which liquid components are produced by the culturing of stem cells. Originally, SHED-CM therapy was developed based on research by Ueda M, et al.18 CM was originally made from stem cells of bone marrow, fat and umbilical cord. Recently, it has been reported that the CM of stem cells from deciduous or permanent dental pulps contains a large number of proteins and cytokines.8,19
5 | CONCLUSION
This is the first clinical report of ED treatment in the literature with the use of SHED-CM. Treatment with SHED-CM is expected to repair vascular damages of the corpus cavernosum, which are the main cause of ED, and to be widely spread as a fundamental clinical application for ED patients.
