Our portfolio includes a variety of different application for exosome-based therapeutics in oncology, cardiology as well as cosmetic applications. We are advancing multiple pipelines utilizing exosome as a target and as a therapeutic. Xollen is currently working on multiple preIND applications to initiate human clinical trials.
Stem Cell Biomimetic Microparticles
As a novel biomimetic therapeutic nanoparticle, PINC offers the following advantages compared to natural stem cells:
Systemic administration: the nanometer size of PINC enables intravenous application; unlike stem cells, PINCs are less likely to clog the lungs.
Dual targeting: the platelet membrane on PINCs enhances targeting to the injured blood vessels while the PGE2 enhances targeting to the injured cardiomyocytes in I/R injury.
Stability: unlike real stem cells, PINCs can be readily manipulated and cryopreserved since there are no living components.
Platelet Vesicles-Engineered Cells and Extracellular Vesicles for Targeted Tissue Repair
Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites
Targeting Regenerative Exosomes to Myocardial Infarction
Cardiac stem cell-derived exosomes have been demonstrated to promote cardiac regeneration following myocardial infarction in preclinical studies. We demonstrated a novel method for increasing delivery of therapeutic exosomes to the site of injury using targeting peptide. Cardiac homing peptide (CHP) targets intravenously-infused exosomes to the injured heart.
Therapeutic Microparticles With Biomimetic Cardiac Stem Cell Membranes and Secretome
A synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. CMMPs act as ‘synthetic stem cells’ which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration.
Synthetic Mesenchymal Stem Cells
We aim to fabricate synthetic analogs of stem cells and test their therapeutic potential for the treatment of acute myocardial infarction in mice. We successfully fabricated a synMSC therapeutic particle and demonstrated its regenerative potential in mice with acute myocardial infarction. The synMSC strategy may provide novel insight into tissue engineering for treating multiple diseases.
Dysregulation in Exosomes Derived From Heart Failure Patients
The constitution of exosomes, as well as their biological activity, largely depends on the cells that secrete them. The heart failure pathological condition altered the miR cargos of cardiac-derived exosomes and impaired their regenerative activities. miR-21-5p contributes to exosome-mediated heart repair by enhancing angiogenesis and cardiomyocyte survival through the phosphatase and tensin homolog/Akt pathway.
3D Cultured Derived Exosomes Promotes Hair Growth
Three-dimensional (3D) cultured dermal papilla spheroids can restore hair inductive capacity. The injection of dermal papilla spheroids promotes the hair follicle cycle from catagen to anagen by paracrine effects (bFGF and exosomes).
Tumor Cell Derived Exosomes Home to Their Parent Tumor
Here we demonstrate that exosomes from cancer
cells fuse preferentially with their parent cancer cells in vitro. Systematic injection of mouse tumor-derived exosomes home to their original tumor tissues in vivo. Moreover, exosomes derived from cancer cells were engineered to carry Doxil, a common chemotherapy drug, to specifically target at their parent tumor site.
Needle-Free Injection of Exosomes Ameliorates Skin Photoaging
Human dermal fibroblasts (HDFs), the main cell population of the dermis, gradually lose their ability to produce collagen and renew the intercellular matrix with aging. The efficacy of 3D HDF-XOs in inducing collagen synthesis and anti-aging was demonstrated in vitro and in a nude mouse photoaging model. 3D HDFs-XOs caused increased procollagen type I expression and a significant decrease in MMP-1 expression, mainly through the downregulation of tumor necrosis factor-alpha (TNF-α) and the upregulation of transforming growth factor-beta (TGF-β). Exosomes from 3D cultured HDF spheroids have anti-skin-aging properties and the potential to prevent and treat cutaneous aging.