I had the honor of interviewing Dr. Bruce Werber about the regenerative applications of placental tissue allografts. In addition to being a board certified foot and ankle surgeon for 35 years, Dr. Werber is the COO of BioTech, Products, Services and Research (BPSR) and the CEO of its subsidiary Anu Life Sciences.
Dr. Werber and I attended the World Stem Cell Summit in Palm Beach, Florida, where we connected over the topic of placental cell applications. I am confident that you will find great value in his insights into the regenerative applications of placental tissues.
Interview with Dr. Bruce Werber, COO of BPSR and CEO of Anu Life Sciences
Cade Hildreth: What is your background and how did you become involved with regenerative applications of placental cells?
Dr. Bruce Werber: I have been a board certified foot and ankle surgeon for 35 years, treating hundreds of patients with diabetic neuropathy and charcot arthropathy wounds. This combination of issues presented me with extremely difficult wounds. Over the 35 years, I had worked with various iterations of platelet rich plasma (PRP). In 2011, I became interested in the potential of placental tissue for healing wounds after reading several articles from the ophthalmology specialty.
In 2011-12, I found a source for a cryopreserved product. At the time, I had several patients who were on the road to lower extremity amputation due to their wounds and multiple co-morbidities. One of those patients was willing to try anything to avoid amputation of his leg. I presented him with the option of using placental tissue, and he jumped at the opportunity. The patient’s wound that was unresponsive for 3 years experienced 20% improvement in the wound size and a 50% reduction of the circumferential lymphedema with 5 days.
After a second application of placental tissue and a total of 63 days, the wound was closed.
By 90 days after first application, the patient was wearing a fairly normal shoe and was able to be put on the kidney transplant list, return to work, and resume life.
After that success, I treated 19 more patients, during which time I developed an injection technique to put the placental tissue into the surrounding healthy tissue and observed incredible rates of wound healing. I published my findings in the Journal of Foot & Ankle Surgery 2013.
Subsequently I went on to form a new company and create a different process to bring placental tissue to a variety of medical and surgical specialties. In working with placental tissue, I worked with an incredible team to be able to assay the tissue growth factors and cellular components and start evaluating the components of the extracellular matrix.
Cade Hildreth: What are unique traits of placental cells, relative to stem and progenitor cell types derived from other tissues?
Dr. Bruce Werber: In my opinion, it is not the placental cells that are the differentiators, but the other factors that give placental allografts a significant edge over the adipose/bone marrow and PRP regenerative tissues.
Yes, there are mesenchymal stem cells in cryopreserved placental tissue allografts that are fully functional after cryopreservation, including fibroblasts, keratinocytes, and epithelial cells. More importantly, what placental tissue contributes is the full function and broad spectrum of growth factor proteins that fuel the regenerative process. In addition to these growth factors, there are microRNA and exosomes present in placental tissue that work in the messaging process to recruit and up-regulate the recipient’s own cellular response.
Last but not least, the extracellular matrix contributes the collagen substrates, laminin and fibronectin, providing a scaffold for tissue growth and regeneration, as well as offering a regulatory mechanism for tissue growth. Additionally, we have documented properties of the placental tissue as providing an antimicrobial environment. This cell regulatory function appears to supply anti-tumorgenic capability and immunomodulating capacity.
With a 100 year history of case series and peer reviewed papers demonstrating safety and efficacy, we need to produce higher level studies. All of these aspects are still under exploration, but it is clear that placental tissue allografts can exert powerful regenerative effects through a variety of mechanisms. The role of each of these factors will become clearer as research into placental tissue expands.
Cade Hildreth: How are placental cells being used clinically in veterinary applications?
Dr. Bruce Werber: Placental allografts are being used for a wide variety of veterinary indications. Within equine (horse) and canine (dog) applications, eye injuries are the leading application, followed by acute and chronic wound applications. Orthopedic indications of tendinopathies, fascial, and joint injuries are also important.
Finally, placental cells are being used in surgical repair to reduce adhesions and fibrosis complications.
Cade Hildreth: How are placental cells being used clinically in human applications?
Dr. Bruce Werber: As with the veterinary side, human clinical indications involving placental stem cells and tissue appear to be starting with wounds, followed by orthopedic conditions to reduce inflammation and pain, in multiple joint areas. They are also being used for tendinopathies and fascial injuries. Multiple surgical intervention pilot studies have shown significant accelerated healing rates and a significant reduction in complications.
Finally, placental tissue allografts are being used in surgical repairs to reduce adhesions and fibrosis and other complications that without these allografts, typically would see high re-operation rates.
Cade Hildreth: What applications show promise and could be addressed in the future using placental tissue allografts?
Dr. Bruce Werber: I believe we will see clinical studies showing promise in the area of neurodegenerative diseases, and improved outcomes in several different surgical specialties where scar, adhesions, and fibrosis cause a high number of repeat surgical episodes using placental tissue allografts.
Cade Hildreth: What companies are working in the area of placental tissue allografts?
Dr. Bruce Werber: Companies working in this space include:
There are also several academic sites doing bench research and clinical studies.
Cade Hildreth: What do you think the next 5-10 years will hold for the placental cells and their use in regenerative medicine?
Dr. Bruce Werber: I think we will see a much better understanding of the mechanisms of action that support the regenerative effects of placental tissue, most likely a breakdown of the components present within the tissue and the creation of allografts to address specific issues.
Cade Hildreth: What regulatory issues affect placental tissue allografts?
Dr. Bruce Werber: There needs to be more study on this subject. I believe the FDA needs to meet with key stakeholders and researchers more frequently to develop better guidelines. Guidelines based on science, not hypothetical issues. They also should take into account the 100 years of anecdotal case series that have been published about the use of placental tissues.
We are in an age of evidenced based medicine, but we cannot discount the safety record of using this tissue. We do need to complete the appropriate clinical level 2 or better EBM type studies, and adjust regulatory compliance based on solid studies. However, for now the incredible safety record should be considered, and the guidelines should reflect the history of safety.
Currently the placental tissue allografts on the market are being used as “361” tissues that are minimally manipulated and intended for homologous use. However, the definitions provided are ambiguous and need more clarity and certainly a better scientific basis than has been provided so far by regulatory agencies.
Cade Hildreth: What other types of perinatal tissues show promise for regenerative medicine applications?
Dr. Bruce Werber: I think there is potential to use portions of the umbilical cord and the maternal portion of the placenta (chorion), but we will need to ensure that all of the markers of self (i.e. Human Leukocyte Antigens) are eliminated to avoid issues with potential graft host reactions. That is why we focus most of our work on using only amniotic fluid and amniotic membrane for allografts being placed into a recipient.
Certainly using the chorion and umbilical tissues topically are not as large of a concern, but if they were to be used as an injectable or intraoperatively, substantial caution would be needed.
Cade Hildreth: How can people get in touch you with to learn more about placental stem cells and their uses in regenerative medicine?
Dr. Bruce Werber: I presently am the COO of BioTech, Products, Services and Research (BPSR) and the CEO of its subsidiary Anu Life Sciences. My email is [email protected].