ICMS Editorial

A Response to the Nagy and Quaggin Opinion on the Angiomyeloproliferative Lesions Following Autologous Stem Cell Therapy by Thirabanjasak et al.
The dangers of stem cell therapy; is the hysteria warranted?

To the editor:

As stem cell treatments proliferate in the future it will be important to separate stem cell related complications from procedural complications.  With this in mind, we read with interest the submission by Thirabanjasak et al. entitled, “Angiomyeloproliferative Lesions Following Autologous

Stem Cell Therapy” in which the authors described the clinical course and ultimately the demise of a patient with end stage renal disease subsequent to lupus nephritis.([i]) The patient received an unconventional therapy consisting of multiple unguided injections of autologous G-CSF mobilized CD34+ hematopoietic progenitor cells directly into the abdominal cavity, presumably targeting the kidneys. The injections were unhelpful and the patient began dialysis within a few months thereafter. After six months the patient presented with abdominal pain at the site of HSC injection, and subsequent imaging revealed a suspected urothelial cell carcinoma. At 11 months after the stem cell treatment the left kidney was resected. Histopathology revealed multiple benign angiomyeloproliferative lesions at or near the injection sites, which the authors concluded arose directly and/or indirectly from the stem cell injections. The patient ultimately died of sepsis associated with a post-nephrectomy AV shunt insertion.

Although the paper was interesting and an important report, what got our attention was the simultaneously published opinion piece by Nagy and Quaggin. These authors took the opportunity to speculate that the stem cell treatment precipitated the patient’s demise, despite the fact that Thirabanjasak et al. did not reach the same conclusion. The authors further claimed that clinics in many countries are performing stem cell transplantation procedures on patients with no oversight and little scientific, pre-clinical or medical rationale, but provided no basis or quantification for their claims. Nagy and Quaggin concluded with the assertion that all stem cell therapies require oversight from the scientific stem cell community and specifically from their organization, the International Society for Stem Cell Research (ISSCR).

These authors bring to the fore a substantial rift in the philosophical and scientific approach to the rapidly expanding field of adult autologous stem cell (A-ASC) therapy. The ISSCR approach to the therapeutic application of A-ASCs is that they be treated in the same manner as a new drug, and thus must be subjected to same investigational research protocols, multiphase trials, and FDA oversight as any drug intended for mass production and interstate distribution prior to introduction to the market. Although such a scenario would make for many busy labs and basic science researchers for many years, and likely generate many patentable products along the way, there could be little practical advancement in medical therapeutics during this process.

As representatives of the Board of Directors of the International Cellular Medicine Society (ICMS) we take issue with and disagree with the claims of Nagy and Quaggin, as well as the position of the ISSCR. The ICMS is dedicated to patient safety and education regarding the medical use of adult stem cells.  Representing over 1,000 physicians, researchers and patients from over 35 countries on 6 continents the ICMS maintains a stem cell treatment registry that tracks long-term complications and outcomes of therapies from participating clinics. It provides clinicians and patients an overview of the nature and extent of the practices of medical clinics that offer stem cell therapy internationally. Additionally, based on the collective experience of its researcher and clinician members, the ICMS has published detailed laboratory and clinical guidelines for medical therapies involving A-ASCs. All clinics associated with the ICMS are obliged to follow these guidelines. Under the ICMS guidelines the therapy described by Thirabanjasak et al. would have been impermissible.

Nagy and Quaggin support their position that stem cell therapy is potentially dangerous and thus must be overseen by their organization with an unjustified interpretation of the facts in the case study. They claim that the described adrenal and liver masses were suggestive of metastasis (the most onerous complication for any stem cell therapy) despite the complete absence of any corroboration by the authors of the case study. In fact, Thirabanjasak et al. concluded that the histopathology of the renal lesions was benign and exhibited normal cytogenetics, and that the patient exhibited no other systemic signs of neoplasm. Certainly, the stem cell injections did nothing beneficial for the patient, and the actions of the clinicians involved with the patients’ care were patently reckless, as blindly injecting stem cells into a patient’s abdomen in the hope that they will reach a diseased organ is not a reasonable medical practice. Interestingly, data from a recent 13 patient pilot study with a one-year follow up has shown that the use of mesenchymal stem cells delivered via an IV route, an approach which has been tested and validated in both pre-clinical and clinical settings (vs blindly injected hematopoietic stem cells used in Thirabanjasak et al.), resulted in a lasting therapeutic benefit to the renal and extra renal symptoms of lupus, with no adverse events reported ([ii]). While the headlines “Stem therapy causes cancer” or “stem cell therapy kills patient” are an effective way to whip up hysteria, they don’t have an origin in the reasonable interpretation of any of the facts in the present case study. Clinical studies are demonstrating safety and efficacy of autologous stem cell therapies in a number of applications ([iii],[iv],[v]). While caution is always justified when evaluating an emerging therapy, the large majority of publications on the topic suggest cautious optimism for continued success with the selective clinical application of A-ASC therapy. It cannot reasonably be argued that there is a public health rationale for discontinuing similar clinical investigations.

We deplore the medical practices that contributed to this patient’s demise, although the described misuse of stem cell therapy did not appear to have led to the patient's demise, directly or indirectly. It is reasonable to ask why Nagy and Quaggin felt that such an interpretation was warranted.

Michael D Freeman PhD MPH
Department of Public Health & Preventive Medicine,
Oregon Health & Science University School of Medicine

Yael Porat PhD
Sanz Medical Center Laniado Hospital, Netanya, Israel

Dori Naerbo, Ph.D.
Reuvenare LLC, Naples, Florida, USA

Michael Belkin, MA, MD
Goldschleger Eye Research Institute, Tel Aviv University, Israel

Sean S Kohles, Ph.D.
Department of Mechanical & Materials Engineering,
Portland State University, Portland, OR

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