We believe that the paracrine effect, in which somatic stem cells release various exosomes, influences the cellular niche, leading to tissue repair and regeneration. Therefore, we are conducting research to maximize this paracrine effect in regenerative therapy.
The paracrine effect refers to the phenomenon where secretions from cells directly affect neighboring cells through diffusion, among other means.
On the other hand, when it acts on distant cells via the systemic circulation, it is called the endocrine effect.
The stem cell culture supernatant necessary for the paracrine effect is derived from stem cells such as dental pulp, bone marrow, adipose tissue, and umbilical cord, with deciduous teeth reported to have particularly high levels of bioactive substances.
Of particular interest to us are exosomes (tiny particles with a diameter of approximately 50nm to 150nm secreted by most cells), and in collaboration with Professor Takahiro Otani of Tokyo Medical University, among others, at our affiliate company DEXON Pharmaceuticals Co., Ltd., we are conducting research.
Exosomes are known to alter cells by exchanging information with distant cells or tissues, and are involved in responses to immunity against viruses and tumors, cell repair, and neurotransmission.
They are considered a type of extracellular vesicle, which also includes microvesicles and apoptotic bodies, each with different mechanisms of production.
Recent research has shown that microRNAs encapsulated in exosomes or extracellular vesicles vary between cells and can transmit both beneficial and detrimental information to recipient cells.
Therefore, exosomal RNA is attracting attention as a biomarker for various diseases, including cancer.
Furthermore, circulating RNA, including protein-bound RNA and free-circulating RNA (fc-RNA), is present in body fluids and cell culture supernatants, leaking from cells due to apoptosis or necrosis.
RNA molecules within exosomes or RNA molecules bound to proteins (fc-RNA) can be extracted from body fluids or cell culture supernatants, providing a wealth of information for disease monitoring.
According to a paper by Takeshi Katsuta and Takahiro Otani from the Molecular and Cellular Therapy Research Field at the National Cancer Center Research Institute, the following description regarding renal diseases is provided:
“In renal diseases, it has been known from studies using various models of acute kidney injury that transplanted MSCs (mesenchymal stem cells derived from the mesodermal connective tissue with multipotent capabilities) act paracrinally on surviving epithelial cells to support tissue regeneration.
Interestingly, the therapeutic effects mediated by exosomes were suggested to involve mRNA transfer. Among these mRNAs are many involved in transcriptional control, proliferation, and immune regulation, suggesting their contribution to tissue regeneration induction.
Subsequent experiments using different animal models have also reported therapeutic effects of MSC-derived exosomes on both acute and chronic kidney injuries.”
Reference: Potential Applications of Mesenchymal Stem Cell-Derived Exosomes in the Development of Novel Therapeutics
URL: https://www.jstage.jst.go.jp/article/dds/29/2/29_140/_pdf
In his recent work, Professor Otiya writes:
“There are also exosomes that perform beneficial functions within the body. These are exosomes secreted from mesenchymal stem cells, which have been a topic of discussion in the field of regenerative medicine. Recently, it has become increasingly clear that many of the disease- and wound-healing abilities of mesenchymal stem cells are mediated by exosomes.” (Katsuda & Ochiya, StemCell Res Ther, 2015).
Furthermore, internationally, in countries such as Singapore and the United States, clinical trials have been initiated to apply exosomes derived from mesenchymal stem cells for disease treatment, and they have been administered to humans. This is indeed a beacon of hope for patients with diseases that current standard treatments cannot effectively address, and for refractory diseases. We hope that by establishing the regulatory science of exosomes, the scientific evidence for their healing effects will be demonstrated, and their clinical application will advance.
※ Exosomes are membrane vesicles with a diameter of approximately 50 to 150 nm secreted by most cells. They are observed in body fluids such as saliva, blood, urine, amniotic fluid, and malignant ascites, as well as being secreted from cultured cells. In recent years, exosomes have been suggested to play a role in transmitting information between distant cells or tissues.
※ The hematopoietic stem cell niche is a microenvironment created by hematopoietic stem cells and supporting cells in the bone marrow.
