Theranostics | April 30, 2021

TGF-β loaded exosome enhances ischemic wound healing in vitro and in vivo

With over seven million infections and $25 billion treatment cost, chronic ischemic wounds are one of the most serious complications in the United States. The controlled release of bioactive factor enriched exosome from finbrin gel was a promising strategy to promote wound healing.

Biotechnol Bioengineering | August 4, 2023

Dose-response analysis after administration of a human platelet-derived exosome product on neurite outgrowth in vitro

Modulating the nerve’s local microenvironment using exosomes is proposed to enhance nerve regeneration. This study aimed to determine the optimal dose of purified exosome product (PEP) required to exert maximal neurite extension. An in vitro dorsal root ganglion (DRG) neurite outgrowth assay was used to evaluate the effect of treatment with (i) 5% PEP, (ii) 10% PEP, (iii) 15% PEP, or (iv) 20% PEP on neurite extension (N = 9/group), compared to untreated controls. After 72 h, neurite extension was measured to quantify nerve regeneration. Live cell imaging was used to visualize neurite outgrowth during incubation. Treatment with 5% PEP resulted in the longest neurite extension and was superior to the untreated DRG (p = 0.003). Treatment with 10% PEP, 15% PEP, and 20% PEP was found to be comparable to controls (p = 0.12, p = 0.06, and p = 0.41, respectively) and each other. Live cell imaging suggested that PEP migrated towards the DRG neural regeneration site, compared to the persistent homogenous distribution of PEP in culture media alone. 5% PEP was found to be the optimal concentration for nerve regeneration based on this in vitro dose–response analysis.

Plastic and Reconstructive Surgery | March 14, 2023

Enhancing Functional Recovery after Segmental Nerve Defect using Nerve Allograft treated with Plasma-Derived Exosome

Nerve injuries can result in detrimental functional outcomes. Currently, autologous nerve graft offers the best outcome for segmental peripheral nerve injury. Allografts are alternatives, but do not have comparable results. This study evaluated whether plasma-derived exosome can improve nerve regeneration and functional recovery when combined with decellularized nerve allografts.

Regenerative Medicine, Vol. 18, NO. 1 | October 18, 2022

Purified exosome product enhances chondrocyte survival and regeneration by modulating inflammatory and promoting chondrogenesis.

This study was to detect the effects of purified exosome product (PEP) on C28/I2 cells and chondrocytes derived from osteoarthritis patients. 

Discovery’s Edge| October 12, 2022

Early Research Toward a Cell-Free Solution for Stress Urinary Incontinence

The research team used regenerative purified exosome product, known as PEP, derived from platelets to deliver messages into the cells of preclinical models. Exosomes are extracellular vesicles that are like a delivery service moving cargo from one cell to another, with instructions for targeting exact tissues that need repair. The study suggests that the use of purified exosome product alleviates stress urinary incontinence from musculoskeletal breakdown in animals. The team did not detect any infection or off-target toxicity with application of PEP

Regenerative Medicine, Vol. 17, NO. 11 | October 4, 2022

Platelet-derived Exosomes Induce Cell Proliferation and Wound Healing in Human Endormetrial Cells.

Aim: To investigate the regenerative effects of a platelet-derived purified exosome product (PEP) on human endometrial cells. Materials & methods: Endometrial adenocarcinoma cells (HEC-1A), endometrial stromal cells (T HESC) and menstrual blood-derived stem cells (MenSC) were assessed for exosome absorption and subsequent changes in cell proliferation and wound healing properties over 48 h. Results: Cell proliferation increased in PEP treated T HESC (p < 0.0001) and MenSC (p < 0.001) after 6 h and in HEC-1A (p < 0.01) after 12 h. PEP improved wound healing after 6 h in HEC-1A (p < 0.01) and MenSC (p < 0.0001) and in T HESC between 24 and 36 h (p < 0.05). Conclusion: PEP was absorbed by three different endometrial cell types. PEP treatment increased cell proliferation and wound healing capacity.

NJP Regen. Med | September 29, 2022

Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence.

Urinary incontinence afflicts up to 40% of adult women in the United States. Stress urinary incontinence (SUI) accounts for approximately one-third of these cases, precipitating ~200,000 surgical procedures annually. Continence is maintained through the interplay of sub-urethral support and urethral sphincter coaptation, particularly during activities that increase intra-abdominal pressure. Currently, surgical correction of SUI focuses on the re-establishment of sub-urethral support. However, mesh-based repairs are associated with foreign body reactions and poor localized tissue healing, which leads to mesh exposure, prompting the pursuit of technologies that restore external urethral sphincter function and limit surgical risk. The present work utilizes a human platelet-derived CD41a and CD9 expressing extracellular vesicle product (PEP) enriched for NF-κB and PD-L1 and derived to ensure the preservation of lipid bilayer for enhanced stability and compatibility with hydrogel-based sustained delivery approaches. In vitro, the application of PEP to skeletal muscle satellite cells in vitro drove proliferation and differentiation in an NF-κB-dependent fashion, with full inhibition of impact on exposure to resveratrol. PEP biopotentiation of collagen-1 and fibrin glue hydrogel achieved sustained exosome release at 37 °C, creating an ultrastructural “bead on a string” pattern on scanning electron microscopy. Initial testing in a rodent model of latissimus dorsi injury documented activation of skeletal muscle proliferation of healing. 

Orthopaedic Journal of Sports Medicine| December 2021

Intrinsic Tendon Regeneration After Application of Purified Exosome Product: An In Vivo Study.

Female Pelvic Medicine & Reconstructive Surgery | October 2021

(FPMRS) Exosome-induced vaginal tissue regeneration in a porcine mesh exposure model.

The purpose of this study was to explore the utility of an injectable purified exosome product derived from human apheresis blood to (1) augment surgical closure of vaginal mesh exposures, and (2) serve as a stand-alone therapy for vaginal mesh exposure.

Biomaterials | September 2021

Effects of purified exosome product on rotator cuff tendon-bone healing in vitro and in vivo.

Exosomes have multiple therapeutic targets, but the effects on healing rotator cuff tear (RCT) remain unclear. As a circulating exosome, purified exosome product (PEP) has the potential to lead to biomechanical improvement in RCT. Here, we have established a simple and efficient approach that identifies the function and underlying mechanisms of PEP on cell-cell interaction using a co-culture model in vitro. 

Plastic and Reconstructive Surgery | August 2021

Administration of purified exosome product in a rat sciatic nerve reverse autograft model.

The nerve autograft remains the gold standard when reconstructing peripheral nerve defects. However, although autograft repair can result in useful functional recovery, poor outcomes are common, and better treatments are needed. The purpose of this study was to evaluate the effect of purified exosome product on functional motor recovery and nerve-related gene expression in a rat sciatic nerve reverse autograft model.

Female Pelvic Medicine & Reconstructive Surgery | March 1, 2021

(FPMRS) Impact of repeat dosing and mesh exposure chronicity on exosome-induced vaginal tissue regeneration in a porcine mesh exposure model.

 The aim of the study was to compare vaginal wound healing after exosome injection in a porcine mesh exposure model with (1) single versus multiple dose regimens and (2) acute versus subacute exposure.

Regen Med | February 24, 2021

(Review) Regenerative medicine clinical readiness.

Regenerative medicine, poised to transform 21st century healthcare, has aspired to enrich care options by bringing cures to patients in need. Science-driven responsible and regulated translation of innovative technology has enabled the launch of previously unimaginable care pathways adopted prudently for select serious diseases and disabilities. The collective resolve to advance the design, manufacture and validity of affordable regenerative solutions aims to democratize such health benefits for all. The objective of this Review is to outline the framework and prerequisites that underpin clinical readiness of regenerative care. Integrated research and development, specialized workforce education and accessible evidence-based practice implementation are at the core of realizing an equitable regenerative medicine vision.

Journal of Orthopaedic Research | September 16, 2020

A novel engineered purified exosome product patch for tendon healing: An explant in an ex vivo model.

Reducing tendon failure after repair remains a challenge due to its poor intrinsic healing ability. The purpose of this study is to investigate the effect of a novel tissue-engineered purified exosome product (PEP) patch on tendon healing in a canine ex vivo model. Lacerated flexor digitorum profundus (FDP) tendons from three canines’ paws underwent simulated repair with Tisseel patch alone or biopotentiated with PEP. For the ex vivo model, FDP tendons were randomly divided into three groups: FDP tendon repair alone group (Control), Tisseel patch alone group, and the Tisseel plus PEP (TEPEP) patch group. Following 4 weeks of tissue culture, the failure load, stiffness, histology, and gene expression of the healing tendon were evaluated. Transmission electron microscopy revealed that in exosomes of PEP the diameters ranged from 93.70 to 124.65 nm, and the patch release test showed this TEPEP patch could stably release the extracellular vesicle over 2 weeks. The failure strength of the tendon in the TEPEP patch group was significantly higher than that of the Control group and Tisseel alone group. The results of histology showed that the TEPEP patch group had the smallest healing gap and the largest number of fibroblasts on the surface of the injured tendon. Quantitative reverse transcription polymerase chain reaction showed that TEPEP patch increased the expression of collagen type III, matrix metallopeptidase 2 (MMP2), MMP3, MMP14, and reduced the expression of transforming growth factor β1, interleukin 6. This study shows that the TEPEP patch could promote tendon repair by reducing gap formation and inflammatory response, increasing the activity of endogenous cells, and formation of type III collagen.

Journal of Orthopaedic Research | January 12, 2020

Characterization of a purified exosome product and its effects on canine flexor tenocyte biology.

Flexor tendon injuries and tendinopathy are very common but remain challenging in clinical treatment. Exosomes-based cell-free therapy appears to be a promising strategy for tendon healing, while limited studies have evaluated its impacts on tenocyte biology. The objective of this study was to characterize a novel purified exosome product (PEP) derived from plasma, as well as to explore its cellular effects on canine tenocyte biology. The transmission electron microscope revealed that exosomes of PEP present cup-shaped structures with the diameters ranged from 80 to 141 nm, and the NanoSight report presented that their size mainly concentrated around 100 nm. The enzyme-linked immunosorbent assay kits analysis showed that PEP was positive for CD63 and AChE expression, and the cellular uptake of exosomes internalized into tenocyte cytoplasm was observed. The cell growth assays displayed that tenocyte proliferation ability was enhanced by PEP solution in a dose-dependent manner. Tenogenic phenotype was preserved as is evident by that tendon-related genes expression (SCX, COL1A, COL3A1, TNMD, DCN, and MKX) were expressed insistently in a high level, while tenocytes were treated with 5% PEP solution. Furthermore, migration capability was maintained and total collagen deposition was increased. More interesting, dexamethasone-induced cellular apoptosis was attenuated during the incubation of tenocytes with a 5% PEP solution. These findings will provide the basic understandings about the PEP, and support the potential use of this biological strategy for tendon healing.

European Heart Journal | April 1, 2019

(Review) Regeneration for All: An Odyssey in Biotherapy: Authors from the Mayo Clinic discuss the evolution of the regenerative paradigm and look to the future.

Two decades ago, if you were to ask a scientist what it would mean to regenerate the heart, you would regularly hear about the power of developmental biology in decoding the intricacy of organogenesis and the plasticity of stem cells recognized as nature’s ultimate ‘building blocks’. The conversation would then delve into the merits and drawbacks of embryonic stem cell technology, presented as the quintessential regenerative phenotype.

With an ever-broader scholarly engagement and a growing public awareness, the academic intrigue of stem cell-based therapy was exponentially fuelled by the practicality of mining adult stem cell reservoirs out of bone marrow and adipose tissue. Universally, this multinational transdisciplinary endeavour captured the imagination of patients and physicians/scientists alike, while recognizing the ensuing medical, ethical and societal opportunities, and potential risks.

The prospect of pioneering a change in disease management propelled this maturing field from science fiction to the rigor of the scientific bench and onwards to randomized clinical trials. Here, the tantalizing concept of rebuilding the body to reverse underlying pathology, as opposed to a battle to palliate disease, emerged as a paradigm shift. In parallel, the notion of a curative intervention held the promise of altering the economics of chronic disease management, relieving the health care system of the cost burden associated with an ageing population vulnerable to degenerative disease.