【English】Human Stem Cell Culture Supernatant (Exosome-Enriched) Therapy

Growth factors and cytokines are signaling molecules that regulate cellular activity by modulating gene transcription within the cell nucleus, thereby initiating a wide range of physiological responses throughout the body. Growth factors, in particular, play essential roles in numerous biological processes in adults, including cell proliferation, differentiation, and apoptosis, as well as immune modulation, hematopoiesis, angiogenesis, metabolism, wound healing, and maintenance of tissue homeostasis. These signals are typically released in response to stimuli received by the secreting cells and act upon specific target cells to exert their physiological effects.

Exosomes are a type of extracellular vesicle (EV) secreted by cells, and they contain biologically active substances such as growth factors and signaling molecules essential for tissue regeneration and intercellular communication. Exosomes play a vital role in mediating cell-to-cell signaling and have gained increasing attention for their therapeutic potential in various disease states. In the field of regenerative medicine, exosomes derived from mesenchymal stem cells (MSCs) are of particular interest. These MSC-derived exosomes exhibit a broad spectrum of therapeutic effects, including anti-inflammatory and anti-fibrotic actions, promotion of angiogenesis, and acceleration of tissue repair. As such, they are regarded as promising tools for “cell-free therapy”—an emerging concept in regenerative treatment.
For example, in myocardial infarction models, MSC exosomes have been shown to suppress cardiomyocyte apoptosis, promote new blood vessel formation, and reduce inflammation. In other preclinical models such as chronic kidney disease, pulmonary fibrosis, and arthritis, MSC-derived exosomes have also demonstrated protective and regenerative effects on tissues.
These beneficial actions are believed to be mediated by the microRNAs (miRNAs) and proteins contained within the exosomes, which modulate gene expression in recipient cells. Given these mechanisms, exosomes are increasingly anticipated to serve as a complement to or even substitute for conventional stem cell therapies.

Several human clinical trials have investigated the use of exosomes and related extracellular vesicles in the treatment of various inflammatory and degenerative conditions. Although the field is advancing rapidly, it is important to recognize that scientific evidence remains under development. Many medical institutions are already offering exosome-based treatments, but at this stage, clinical application should proceed with appropriate caution and rigorous oversight.Examples of Phase 2/3 Trials:
• Efficacy and Safety of EXOSOME-MSC Therapy to Reduce Hyper-inflammation in Moderate COVID-19 Patients Investigating the potential of exosome-based MSC therapy to reduce excessive inflammation in moderate COVID-19 cases.
• Effect of Microvesicles and Exosomes Therapy on β-cell Mass in Type I Diabetes Mellitus (T1DM) Evaluating whether therapy with microvesicles and exosomes can improve or preserve pancreatic β-cell mass in T1DM patients.
• The Effect of Stem Cells and Stem Cell Exosomes on Visual Functions in Patients With Retinitis Pigmentosa Studying the impact of stem cells and their exosomes on visual function in patients with degenerative retinal disease.
• Use of Autologous Plasma Rich in Platelets and Extracellular Vesicles in the Surgical Treatment of Chronic Middle Ear Infections Assessing the clinical outcomes of applying platelet- and EV-rich autologous plasma in surgical management of chronic otitis media.
Example of a Phase 3 Trial:
Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome (ARDS) (EXTINGUISH ARDS) A large-scale trial evaluating the use of extracellular vesicles in patients with ARDS, a life-threatening pulmonary condition.

Product Name: Human Adipose Stem Cell Conditioned Media Extract (Freeze-dried) (Purified extract of human adipose-derived stem cell culture supernatant)
Classification: Research reagent
Origin: This product is a freeze-dried formulation of a purified and concentrated solution derived from the culture medium of human adipose-derived stem cells.
Country of Manufacture: Japan

Appearance: White powder; colorless to pale yellow, odorless solution upon reconstitution
TBU (Total Bioactive Units): ≥120 TBU (ELISA method)
NH₃ (Ammonia): <10 µg/dL (upon dissolution in 2 mL, indicator method)
pH: 7.4 ± 0.3 (upon dissolution in 2 mL, glass electrode method)
Heavy Metals: Not detected (sodium sulfide colorimetric method)
Arsenic: Not detected (atomic absorption spectrophotometry)
Storage Conditions: Store refrigerated (2–6°C) in a sealed container away from direct sunlight
Shelf Life:3 years from the date of manufacture(Once opened, use promptly to avoid contamination.)
Allergens: None contained
GMO Status: Not applicable
Animal-derived Components: Not contained

1.Microbiological Testing
・Sterility Test (SCDLP and GPLP agar plate method): Negative — Compliant
・Mycoplasma Test (Nucleic Acid Testing, NAT): Negative — Compliant
・Endotoxin Test (Gel clot method): <0.015 EU/mL — Compliant
2.Primary Skin Irritation Test(LabCyte EPI-MODEL24 SIT test using a 3D cultured human skin model)
Summary: The test substance showed a cell viability of 101.1 ± 1.1%, well above the 50% threshold, indicating no irritation. Therefore, a 10% solution of the freeze-dried extract was classified as “Not Classified” (non-irritant) for skin irritation.
3.Acute Oral Toxicity Test (Mouse Study)
Summary: A single oral dose of the product dissolved in distilled water (2000 mg/kg) was administered to groups of 5 male and 5 female mice. The animals were observed for 14 days post-administration, with necropsy performed on Day 15. No signs of toxicity were observed at the maximum dose tested.

1）Virus Test Method Result
・Hepatitis B Virus (HBV) HBs Antigen, HBc Antibody (CLIA) Negative — Compliant
・Hepatitis C Virus (HCV) HCV Antibody II (CLIA) Negative — Compliant
・Human Immunodeficiency Virus (HIV) HIV Antigen/Antibody (CLIA) Negative — Compliant
・Human T-cell Leukemia Virus (HTLV-1) HTLV-1 Antibody (CLEIA) Negative — Compliant
・Human Parvovirus B19 (PVB-19) PVB-19 DNA (PCR) Negative — Compliant

2）Human Parvovirus B19 (PVB-19) PVB-19 DNA (PCR) Negative — Compliant
HBV Antigen (HBsAg) CLIA Negative — Compliant (<0.005 IU/mL)
HBV Antibody (HBsAb) CLIA Negative — Compliant (<0.1 COI)
HCV Antibody II CLIA Negative — Compliant (<0.1 COI)
HIV Antigen CLIA Negative — Compliant
HIV Antibody CLIA Negative — Compliant
HTLV-1 Antibody CLIA Negative — Compliant
PVB-19 DNA PCR Negative — Compliant

Source: Manufacturer’s Technical Report