Exosome-based products have the potential to treat many medical conditions and diseases, but further research is needed to know their safety profile. Currently, the only stem cell treatments approved by FDA are products that treat certain cancers and disorders of the blood and immune system. Exosome-related products are used in various therapeutic applications such as gene therapy, vaccine development, tissue regeneration, drug delivery, and as biomarkers in diagnosis and therapy.

The exosome field is experiencing exponential growth due to increased interest and research into exosome roles in disease pathology and potential treatment; however, inconsistency in methodology for the collection, isolation, and analysis of exosomes has created a significant barrier to rapid advancement in the field. The exosome market is divided into three main categories: research/lab, diagnostics, and disease monitoring, and therapeutics. Each of these sectors has its own specific trends, drivers, and challenges, yet they are interconnected and affect further market development. Nevertheless, isolation and purification of exosomes using consistent and reproducible methods remain a challenge. It is challenging to ensure lot-to-lot consistency of the product, and the cargo contained in the exosomes.

Lihan biologics is committed to supporting researchers in finding the best solutions. We start to provide off-the-shelf exosome products that are ready for immediate worldwide delivery. Additionally, our scientists are ready to offer a complete set of services to support your exosome-associated research, such as exosome isolation and purification, exosome analysis and characterization and customizable exosomes for specific downstream applications.
We are evolving our understanding of exosomes and methods of purification and analysis to come up with new diagnostics, and new therapeutics that will improve health broadly for ourselves and our loved ones.

Mesenchymal stem cells (MSCs)

Mesenchymal stem cells (MSCs) have been demonstrated to have a great potential in the treatment of several diseases due to their differentiation and immunomodulatory capabilities and their ability to be easily cultured and manipulated. Exosomes reflect biophysical features of MSCs and are considered more effective than MSCs themselves. Alternative approaches based on MSC-derived exosomes can offer appreciable promise in overcoming the limitations and practical challenges observed in cell-based therapy. Furthermore, MSC-derived exosomes may provide a potent therapeutic strategy for various diseases and are promising candidates for cell-based and cell-free regenerative medicine. MSC-derived exosomes increasingly play an important role in intracellular communication mechanism and tissue repair and their clinical use may supply substantial advantages in comparison with their live cells due to potential to reduce undesirable side effects after application as well as infusional toxicities, uncontrolled cell growth and possible tumor formation. Moreover, exosomes transplantation seems to be less risky and may have several advantages in contrast to cell applications. Exosomes are neither able to mutate and duplicate, nor induce metastasis.

Umbilical cord (UC) MSCs (UC-MSCs)

Umbilical cord (UC) MSCs and their exosomes have extensive potential in regenerative medicine. UC MSC-derived exosomes have been reported to treat CCl4-induced mouse liver fibrosis. It was shown that transplantation of human UC MSC-derived exosomes caused successful decrease of the serum fibrotic marker hyaluronic acid, TGF-β1 and serum aspartate aminotransferase and reduced hepatic inflammation and collagen deposition1. Zhang et al. demonstrated intensive support of cutaneous wound healing and angiogenesis in vivo in a rat model of skin-deep second degree burn wound by human UC MSC-derived exosomes2. Mao et al. demonstrated decrease of pro-inflammatory cytokines IL-6, IL-1β, TNF-α expression and increase of anti-inflammatory cytokine IL-10 expression after UC MSC-derived exosomes treatment in inflammatory bowel disease in a mice model. Interestingly, significant inhibition of IL-7 expression was also observed in the colon mucosa tissues and spleens in a mice model3.

Current advanced therapies for Hair Loss Treatments and associated challenges

Hair loss is a quite common condition observed in both men and women. Pattern hair loss also known as androgenetic alopecia is the most common form of hair loss that is thought to affect up to 80% of Caucasian men and up to 40% of Caucasian women by age of 70, and it can have quite devastating consequences on one’s well-being, including lower self-esteem, depression and lower quality of life.
Several topical, intralesional, oral, and surgical treatments have been developed in recent decades, but some of those therapies only provide partial improvement. Advanced medical therapies are medical products based on genes, cells, and/or tissue engineering products that have properties in regenerating, repairing, or replacing human tissue. In recent years, numerous applications have been described for advanced medical therapies. With this background, those therapies may have a role in the treatment of various types of alopecia such as alopecia areata and androgenic alopecia.
Till date there have only been 2 FDA approved medications, minoxidil and finasteride, but their effects are often unsatisfactory and temporary, in addition to having various adverse effects. As defined by the European Commission, Advanced Therapy Medicinal Products (ATMPs) are new medical products based on genes (i.e., recombinant nucleic acids, gene therapy), cells (cell therapy), and/or tissue engineered products that contain or consist of engineered cells or tissues and are presented as having properties for, or are used in or administered to, human beings with a view of regenerating, repairing, or replacing human tissue.
Stem cell-based therapies have recently received lots of attention as potential novel treatments that focus on reactivating hair follicle stem cells and in this way enhance hair follicle growth, regeneration and development. Stem cell-based therapy approaches include stem cell transplant, stem cell-derived conditioned medium and stem cell-derived exosomes. Stem cell-based therapies for hair loss are still at their infancy and more robust clinical studies are needed to better evaluate their mechanisms of action, efficacy, safety, benefits and limitations.
Stem-cell transplant, demonstrate preclinical and some clinical success, however it is compromised with certain challenges. It is a costly procedure, and also raises concerns for tumorigenicity. Thus UC-MSC derived exosomes are proposed to be more affordable and safer in terms of tumor development.

Current advanced therapies for Diabetic Foot Ulcers treatments and associated challenges:

Diabetic foot ulcers (DFUs) are very important diabetes-related lesions that can lead to serious physical consequences like amputations of limbs and equally severe social, psychological, and economic outcomes. It is reported that up to 25% of patients with diabetes develop a DFU in their lifetime, and more than half of them become infected. Therefore, it is essential to manage infection and ulcer recovery to prevent negatives outcomes. Currently available approaches in the management and treatment of DFUs, including molecular and regenerative medicine, antimicrobial and energy-based therapies, and the use of plant extracts, antimicrobial peptides, growth factors, and nano-medicine. There are various emerging therapies that are different from the standard care for DFUs, whose main objective is to accelerate ulcer healing. Some examples of these treatments are adjuvant growth factors, inflammatory modulators, plant extracts, blood products, biologic therapy, wound negative pressure, hyperbaric oxygen therapy, and skin substitutes. However, these therapies are companion therapies and do not replace standard care for diabetic foot problems.
Cell and gene therapy are in-development techniques used to improve DFU treatments. Stem cells, keratinocytes, and fibroblasts were investigated as treatments for chronic wounds. Stem-cell therapy is employed to increase blood flow in limbs with ischemia. It is thought that this procedure can help to heal chronic wounds. Among the different types of stem cell therapies are mononuclear cells derived from bone marrow and MSCs. MSCs contain multipotent progenitors and can differentiate into several cell lines. In a recent study, MSCs in a collagen matrix were used to assess the progression of DFU healing in a murine model4.

Research on UC-MSCs at Lihan Biologics

We are working on human UC-MSCs derived exosomes-based products for the treatment of

Hair loss
Diabetic foot ulcers

We provide the resources to the latest preclinical studies and a more detailed description of the latest clinical studies concerning stem cell-based therapies for above mentioned.

Cutaneous wound healing is a complex, dynamic process in charge of restoring the structure and function of damaged tissues. It involves highly orchestrated multiple processes including hemostasis, inflammation, cell migration and proliferation, angiogenesis and extracellular matrix remodeling which are strictly regulated by multiple diverse growth factors, cytokines, enzymes and structural matrix proteins generated by multiple cell types such as dermal fibroblasts, epidermal keratinocytes, and immune cells.
Therapies based on UC-MSCs showed great potential for wound healing due to their ability to recruit cells and release growth factors and proteins. In fact, UC-MSCs have been tested as a promising cell-based therapy for diabetic wounds in vitro owing to their ability to accelerate wound closure with increased epithelialization, granulation tissue formation, and angiogenesis by differentiation into skin cells and paracrine pathways to repair injured cells.
The hair follicle cycle is a complex process involving alternating phases of rapid growth (anagen), regression (catagen), and quiescence (telogen). Hair follicles are epidermal appendages that contain both epithelial and mesenchymal compartments. The dermal papilla is located at the base of the hair follicle and plays a fundamental role in the hair follicle cycle. UC-MSCs are able to promote the proliferation of dermal papilla cells in vitro and promote hair growth. UC-MSCs exosomes significantly promoted the conversion of telogen to anagen and increased the thickness of the dermis, which also indirectly reflects the improvement of hair growth.
UC-MSCs based therapy is proposed as a non-toxic treatment option. It is very likely that the role of UC-MSC exosomes in hair follicle dynamics will become a high-impact tool in skin regenerating cosmetics and biomedicine.
Therefore, Lihan Biologics is involved in extensive research for a better understanding of the molecular mechanisms underlying the action and therapeutic potency of UC-MSC exosomes in the clinical context. In order to assess their clinical translation, we are also optimizing and standardizing methods for large-scale production, including the source of MSCs, their isolation and culture conditions as well as the administration protocols for exosomes.

References

Li TF, Yan YM, Wang BY, Qian H, Zhang X, Shen L, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev. 2013;22(6):845–54.
Zhang B, Wu X, Zhang X, Sun Y, Yan Y, Shi H, et al. Human umbilical cord mesenchymal stem cell exosomes enhance angiogenesis through the Wnt4/β-catenin pathway. Stem Cells Transl Med. 2015;4(5):513–22.
Mao F, Wu YB, Tang XD, Kang JJ, Zhang B, Yan YM, et al. Exosomes derived from human umbilical cord mesenchymal stem cells relieve inflammatory bowel disease in mice. Biomed Res Int. 2017;2017:1.
Assi R., Foster T.R., He H., Stamati K., Bai H., Huang Y., Hyder F., Rothman D., Shu C., Homer-Vanniasinkam S., et al. Delivery of mesenchymal stem cells in biomimetic engineered scaffolds promotes healing of diabetic ulcers. Regen.
Med. 2016;11:245–260. doi: 10.2217/rme-2015-0045.