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These days, we so overuse the word ‘innovative’ as to render it meaningless. Yet once in a while someone comes up with such a simple therapy that it truly deserves being called innovative. Developed as a collaboration between Tianhe Stem Cell Biotechnologies Inc. in China and the University of Illinois at Chicago, USA, the Stem Cell Educator is a simple and ingenious use of stem cells for treating autoimmune Type I and inflammatory Type II diabetes.

The idea is simplicity itself. A closed-loop system. Take circulating blood out of an autoimmune diabetes patient, separate out the lymphocytes and park them inside the Stem Cell Educator, a device coated with adherent (sticky) Umbilical Cord Blood Stem cells (CB-SC). The lymphocytes are kept in contact with these adherent CB-SCs for 2 to 3 hours then pumped out of the Stem Cell Educator back into the patient. That’s it, the sum of the entire therapy.

Google Patents shows the group patented the method for isolating the CB-SCs but not the Stem Cell Educator approach, i.e. it appears any interested party is free to test this approach, though I recommend consulting a patent lawyer to make sure there are no IP (Intellectual Property) issues. With Phase I/II clinical trials on patients in China already completed, the open-access journal, BMC Medicine published peer-reviewed trial data.

What’s the Stem Cell Educator? Home – ClinicalTrials.gov identifier: NCT01415726

Modified from Zhao, Yong, et al. “Reversal of type 1 diabetes via islet β cell regeneration following immune modulation by cord blood-derived multipotent stem cells.” BMC medicine 10.1 (2012): 3. Page on biomedcentral.com

Advantages of Stem Cell Educator

  1. Extremely simple treatment so saves cost and time.
  2. As simple as undergoing apheresis. What’s Apheresis? Take a donor’s blood out, pass it through a device, the Blood Cell Separator, that separates out one particular blood cell type, say lymphocytes for example, and returns the rest back to the donor.
  3. Autologous (patient’s own) cells are taken out, treated inside the Stem Cell Educator, and returned back to the patient so inventors claim it carries lower risk of infection compared to a typical blood transfusion.
  4. Fewer safety and ethical concerns compared to other types of treatments so it’s a more versatile and flexible design to treat different types of autoimmune and inflammatory diseases.

Safety concerns according to the inventors
Inventors claim CB-SCs have very low immunogenicity so no need for HLA (Human Leukocyte Antigen) matching. Immunogenicity means propensity to provoke immune responses.

Inventors also claim only patient’s lymphocytes and not CB-SCs are returned back to patient. How could that be? They claim the CB-SCs are adherent, i.e. stuck but good to the FDA-approved hydrophobic material inside the device.

Ethical concerns
Umbilical cord blood is a natural biological product of birth. It’s freely available post-birth. Apart from cord blood bank monthly quotas and parents who choose to bank their cord blood, all other cord blood is freely available for research and therapeutic use. Such blood is subjected to the same screening processes as adult blood, screening for diseases such as HIV, hepatitis, syphilis, etc. Screened cord blood is thus safe for human use.

How does Stem Cell Educator treat autoimmunity?
CB-SCs present unique cell-surface molecules as well as secrete other unique ones. Inventors speculate they interact with the passing lymphocytes and ‘educate’ them. What does ‘educate’ imply here? Lymphocytes are taken from patients diagnosed with autoimmune diseases such as Type I diabetes. They have circulating T cell lymphocytes that recognize protein antigens from the beta-cells of the pancreas. As their T cells progressively destroy their pancreatic beta-cells, i.e. autoimmune pathology, people with diabetes progressively lose their ability to synthesize insulin and thereby the capacity to regulate blood glucose. They need daily injections of insulin to survive. Insulin treats diabetes but doesn’t cure it. The underlying pancreas destruction continues with autoimmune T cells killing off pancreatic beta-cells. Inventors speculate that contact with CB-SCs inside the Stem Cell Educator ‘educates’ such autoimmune T cell lymphocytes to make immune responses that don’t destroy the pancreas.

In my opinion, two alternative explanations exist. One, adherent lymphocytes could bind to CB-SCs and be retained in the device, with only non-adherent lymphocytes returned back to the patient. If CB-SC-adherent lymphocytes were the ones responsible for the autoimmune disease, those returned back to patients would be depleted of such disease-causing cells. Two, few, rare CB-SCs from the Stem Cell Educator could detach and get transfused into the patients. Such cells could actively modulate/regulate anti-pancreas autoimmune responses.

Does Stem Cell Educator treat autoimmune and inflammatory diabetes?
Though preliminary, so far two peer-reviewed open-label phase I/II studies in China show that pancreas function improved in diabetes patients treated just once. Pancreatic islet beta-cell function assessed for several weeks following the procedure showed steady improvement.

The 1st study in 2012 on 15 type I diabetes patients. Pancreas function: compare red/orange lines to blue line.

Modified from Zhao, Yong, et al. “Reversal of type 1 diabetes via islet β cell regeneration following immune modulation by cord blood-derived multipotent stem cells.” BMC medicine 10.1 (2012): 3. Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells

How could we be sure that pancreas function improved in treated patients? Reduced insulin treatment at both 12 and 24 weeks post-treatment, by 38%/25% in patients with moderate/severe loss of pancreatic beta-cell function.

The 2nd study in 2013 on 36 type II diabetes patients. Pancreas function: Orange line rises above dotted red line suggesting pancreas insulin function improves.

Modified from Zhao, Yong, et al. “Targeting insulin resistance in type 2 diabetes via immune modulation of cord blood-derived multipotent stem cells (CB-SCs) in stem cell educator therapy: phase I/II clinical trial.” BMC medicine 11.1 (2013): 160. BMC Medicine | Full text | Targeting insulin resistance in type 2 diabetes via immune modulation of cord blood-derived multipotent stem cells (CB-SCs) in stem cell educator therapy: phase I/II clinical trial

Patients reduced insulin treatment to 35% at 12 weeks post-treatment.

Caveats to bear in mind

  1. There’s no independent data yet from other groups corroborating those from the inventors.
  2. These two studies have limited data sets, only 15 patients in 1st study and 36 in the 2nd one.
  3. Poor description of study statistics. Don’t explain if error bars indicate standard deviation. Would have been more compelling and transparent if they’d shown individual patient responses using scatter plots. For example, are there some patients whose pancreatic beta-cell function doesn’t improve at all? Are there sub-sets of patients, some who respond very well, others moderately, and still others, not at all?
  4. Why are important controls missing in the 2nd study, especially why are there none who received sham therapy?
  5. Need years-long follow-up of patients. Does pancreatic beta-cell function continue to improve, plateau or revert back to disease?
  6. Is one treatment sufficient or are more needed?
  7. Inventors used a method called flow cytometry to examine the cells returned back to the patients from the Stem Cell Educator. Were there any CB-SCs among these cells? Though the inventors claim not, there are two caveats. One, sensitivity cutoff of the method used. Flow cytometry is not sufficiently sensitive to pick up a handful of CB-SCs among billions of lymphocytes. Two, assumption that certain specific cell-surface molecules are uniquely expressed at equally high and unchanged levels in all the CB-SCs at all times. If this were not so, we could no longer rely on such molecules to track these cells.
  8. Critical to figure out exactly how this treatment works.

Even with those caveats, these preliminary human data compellingly suggest that eventually it may be possible to cure previously incurable autoimmune and inflammatory diabetes.

Currently, there are 4 clinical trials in progress, at least those tracked by Home – ClinicalTrials.gov, one for alopecia (autoimmune hair loss), two for type I diabetes, and one for type II diabetes, all sponsored by Tianhe Stem Cell Biotechnologies Inc. in China, alone or in collaboration with the University of Illinois at Chicago, USA or Hebei Medical University First Hospital, China, Second Xiangya Hospital of Central South University, China or the Chinese government.