I wanted to start a new thread specifically on Stem Cell Secretome (SCS). It is a Stem Cell-based regenerative treatment, but without the cells themselves (using their secreted factors instead).
Cell Secretome: Basic Insights and Therapeutic Opportunities for CNS Disorders:
The term secretome was introduced by Tjalsma et al., who defined it as "both the components of machineries for protein secretion and the native secreted proteins". This definition then evolved to a more elaborated concept by Hathout and Agrawal in which the secretome was defined by the factors that are secreted by a cell, tissue, or organism to the extracellular space under a defined time and conditions. Currently, this definition could be updated since it is known that, beyond soluble factors, the secretome also has the presence of lipids and extracellular vesicles (EVs) carrying important molecules.
Especially interesting is this:
Based on the cited studies, it is clear that there is increasing evidence that stem cell secretome can have neuroprotective, neuroregenerative, and immunomodulatory actions. Many studies support the conclusion that the recovery of neural and glial function in CNS trauma and disorders is due to the secretion of soluble factors and vesicles by the transplanted MSCs rather than by cell replacement.
Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice:
Abstract: Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 µg/µL) injection at the same time point; and (ii) UCMSC exosome (1.2 µg/µL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity induced hearing loss by promoting tissue remodeling and repair.
Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo:
The present study provides initial proof of the high potential of UC-MSC-derived EVs to support neuronal survival and to repair noise-induced damage in the inner ear. The capacity to manufacture and characterize clinical-grade EVs under current GMP will support the rapid translation of these research findings into clinical application and may be helpful also for the intervention in other organ systems and disease indications. Even though more research into the mechanism of action of MSC-EVs is needed, our data indicate that clinical grade EVs derived from UC-MSC are highly protective for auditory neurons and can protect the inner ear against noise trauma in vivo. These findings provide a solid foundation for the future use of human stromal cell-derived EVs as a novel cell-free therapeutic approach for the protection of the inner ear.
Some more review articles below. They do not specifically mention hearing loss or tinnitus, but they do talk about the neuroregenerative effects of SCS.
The current landscape of the mesenchymal stromal cell secretome: A new paradigm for cell-free regeneration
The Emerging Role of Exosomes in the Treatment of Human Disorders With a Special Focus on Mesenchymal Stem Cells-Derived Exosomes
This clinic is offering Secretome treatment in Germany:
https://anova-irm.com/en/stem-cell-therapy/secretome-exosomes-therapy
My thinking is (and please correct me if I am wrong! I am a physicist by training so this is definitely not my area) that for cochlear synaptopathy, growth factors released by the stem cells should be the therapeutic agent. In addition, cell-free treatment is supposedly safer. I have 10+ tinnitus noises, hyperacusis and auditory neuropathy (probably just synaptopathy, but they diagnosed it as 'neuropathy' using ABR). It's all a result of two recent acoustic traumas. I have no hearing loss in my audiograms, except for 30 dB at 16 kHz. Otoacoustic emissions normal.
I am having a Skype call with ANOVA IRM this Friday. If all goes well, I will be going for my liposuction in November and Secretome treatment in December. From one adipose tissue sample (10 ml) they can produce 10 doses of Secretome. It can be frozen and stored for up to 2 years, so you can repeat the treatment without the need for harvesting adipose tissue again. They do IV administration, but I will ask for trigger points/intranasal, too. Exosomes (small lipid NPs containing proteins and miRNA) do cross the BBB, so do BDNF and NT3, in smaller quantities, so I hope IV can be sufficient. In the basic treatment plan, they include 1 liposuction, cell separation, growth, Secretome extraction and 3 treatments. The cost is around €20,000 EUR.
I will keep updating this thread with my progress. In the meantime, does anyone have any thoughts about this kind of treatment? I understand that this is more of a shotgun-approach to see what sticks.
Cell Secretome: Basic Insights and Therapeutic Opportunities for CNS Disorders:
The term secretome was introduced by Tjalsma et al., who defined it as "both the components of machineries for protein secretion and the native secreted proteins". This definition then evolved to a more elaborated concept by Hathout and Agrawal in which the secretome was defined by the factors that are secreted by a cell, tissue, or organism to the extracellular space under a defined time and conditions. Currently, this definition could be updated since it is known that, beyond soluble factors, the secretome also has the presence of lipids and extracellular vesicles (EVs) carrying important molecules.
Especially interesting is this:
Based on the cited studies, it is clear that there is increasing evidence that stem cell secretome can have neuroprotective, neuroregenerative, and immunomodulatory actions. Many studies support the conclusion that the recovery of neural and glial function in CNS trauma and disorders is due to the secretion of soluble factors and vesicles by the transplanted MSCs rather than by cell replacement.
Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice:
Abstract: Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 µg/µL) injection at the same time point; and (ii) UCMSC exosome (1.2 µg/µL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity induced hearing loss by promoting tissue remodeling and repair.
Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo:
The present study provides initial proof of the high potential of UC-MSC-derived EVs to support neuronal survival and to repair noise-induced damage in the inner ear. The capacity to manufacture and characterize clinical-grade EVs under current GMP will support the rapid translation of these research findings into clinical application and may be helpful also for the intervention in other organ systems and disease indications. Even though more research into the mechanism of action of MSC-EVs is needed, our data indicate that clinical grade EVs derived from UC-MSC are highly protective for auditory neurons and can protect the inner ear against noise trauma in vivo. These findings provide a solid foundation for the future use of human stromal cell-derived EVs as a novel cell-free therapeutic approach for the protection of the inner ear.
Some more review articles below. They do not specifically mention hearing loss or tinnitus, but they do talk about the neuroregenerative effects of SCS.
The current landscape of the mesenchymal stromal cell secretome: A new paradigm for cell-free regeneration
The Emerging Role of Exosomes in the Treatment of Human Disorders With a Special Focus on Mesenchymal Stem Cells-Derived Exosomes
This clinic is offering Secretome treatment in Germany:
https://anova-irm.com/en/stem-cell-therapy/secretome-exosomes-therapy
My thinking is (and please correct me if I am wrong! I am a physicist by training so this is definitely not my area) that for cochlear synaptopathy, growth factors released by the stem cells should be the therapeutic agent. In addition, cell-free treatment is supposedly safer. I have 10+ tinnitus noises, hyperacusis and auditory neuropathy (probably just synaptopathy, but they diagnosed it as 'neuropathy' using ABR). It's all a result of two recent acoustic traumas. I have no hearing loss in my audiograms, except for 30 dB at 16 kHz. Otoacoustic emissions normal.
I am having a Skype call with ANOVA IRM this Friday. If all goes well, I will be going for my liposuction in November and Secretome treatment in December. From one adipose tissue sample (10 ml) they can produce 10 doses of Secretome. It can be frozen and stored for up to 2 years, so you can repeat the treatment without the need for harvesting adipose tissue again. They do IV administration, but I will ask for trigger points/intranasal, too. Exosomes (small lipid NPs containing proteins and miRNA) do cross the BBB, so do BDNF and NT3, in smaller quantities, so I hope IV can be sufficient. In the basic treatment plan, they include 1 liposuction, cell separation, growth, Secretome extraction and 3 treatments. The cost is around €20,000 EUR.
I will keep updating this thread with my progress. In the meantime, does anyone have any thoughts about this kind of treatment? I understand that this is more of a shotgun-approach to see what sticks.
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