Mari Mitrani, Chief Science Officer, and Michael A. Bellio, Laboratory Director, Organicell (Miami, FL, USA), discuss the progression in cell therapeutics to the nanoscale for improved outcomes after stem cell transplantation in this exclusive interview.
What are the benefits of acellular therapies vs cell-based therapies?
There has been varied success of cell therapies, such as mesenchymal stem cell (MSC) therapies. One of the reasons for this variation is the degree of cell engraftment that occurs after transplantation. In finding limited cell engraftment after transplantation in cell therapies, questions were raised about the mechanism of action for the observed therapeutic effect of cell therapy. Researchers have since found cellular secretions, such as extracellular vesicles (EVs) and exosomes, to mediate the cellular regenerative effect. Isolation of exosomes from in vitro conditioned media or exosome rich fluids has proven to induce similar or even greater regenerative response than the cells themselves. The nanosized nature of exosomes allows for wide-spread distribution and absorption into spaces inaccessible by the cells themselves.
Organicell has developed technologies to isolate and concentrate exosomes from natural and minimally manipulated biological sources. This process reduces the regulatory challenges observed with typical exosome manufacturing techniques that require laboratory expansion of cell lines to produce exosome products. Organicell’s lead biological product Organicell Flow is an acellular, minimally manipulated product derived from perinatal fluid. Organicell Flow is exosome rich, contains hyaluronic acid and has over 300 different soluble growth factors, cytokines and chemokines. Each lot of the product is certified to contain no endotoxin and be negative for aerobic, anaerobic and fungal contamination.
Why do you think we haven’t seen many acellular/EV-based therapies come to market thus far?
Several challenges have slowed the translation of exosomes into clinical trials. These challenges include the qualification of nanoparticle technologies to quantify and characterize the EV/exosome products, development of large-scale production techniques to isolate or produce exosome rich fluids and the large-scale precipitation, concentration and processing of clinical-grade, cGMP compliant exosome products. Scientists have been challenged to develop manufacturing techniques that allow for the scale up production of exosome products proven effective in animal models to meet those quantities and qualifications needed for a safe and effective dose in humans.
Cell therapies, such as MSC therapy, have a long track record with the FDA and have well established manufacturing processes and clinical outcomes. EV/exosome products differ from cell therapies in that there is a large heterogeneity between various EV products that is dependent on manufacturing strategy and tissue or cell origin. The nanosize nature of EV products further create regulatory challenges that require detailed characterization of the molecular components for comparative analysis from one product to another.
Is Organicell autologous or allogeneic and what is the process for sourcing the raw materials?
Organicell’s products are allogeneic and collected from consenting adults who have been screened following FDA guidelines for donor qualification CFR 1271. The perinatal tissue is obtained solely through voluntary donation during planned cesarean sections. Organicell holds an approved institutional review board (IRB) protocol to qualify all donors. Perinatal tissue is collected in the operating room and shipped overnight to the Organicell Manufacturing Facility in Miami, FL, USA. All product manufacturing is performed in a designated clean room space qualified to maintain air quality of ISO-Class 7 with cGMP standards.
What lessons can be applied from the commercialization of previous advanced therapies e.g manufacturing process, supply chain, regulatory pathway etc?
Lessons have been learned from observing the regulatory challenges imposed by the FDA regarding stem cell and other cell-based therapies. EV/exosome therapies are subjected to the same regulatory standards as cell therapies. Product stability, reproducibility, demonstrated safety and potential efficacy are critical considerations that must be made in the commercialization of successful biological products. In the development of Organicell Flow, we had to consider what was the optimal source of regenerative exosomes that could be acquired with the minimal amount of handling and without the addition of non-natural ingredients. Furthermore, we aimed to use only qualified materials and processing equipment in validated manufacturing procedures to consistently produce a stable EV product that meets our release criteria for composition and safety.
Organicell Flow is being trialed in a number of indications, from musculoskeletal to neurology. How does Organicell Flow work on so many cell types and environments?
We believe that the key to Organicell Flow’s therapeutic effect is in the unique nanoparticle composition. Organicell Flow contains a rich collection of perinatal sourced exosomes that contain a variety protein and nucleic acid factors, specifically microRNAs. We have successfully characterized the miRNA composition of Organicell Flow exosomes and found them to target several critical genes contributing to the progression of degenerative diseases such as osteoarthritis, COPD (chronic obstructive pulmonary disease) and SARS (severe acute respiratory syndrome). Many of the indications we are targeting with Organicell Flow contain similar dysregulations in inflammatory pathways. These inflammatory pathways may be modulated by the miRNA and protein rich compositions of perinatal sourced biologics. Our team is working diligently to initiate several investigational new drugs (INDs) and clinical trials to prove these concepts and demonstrate the versatile nature of Organicell Flow.
The opinions expressed in this interview are those of the interviewees and do not necessarily reflect the views of RegMedNet or Future Science Group.