these blog posts are written by Dr. alfredo G. Tomasselli, a Retired bio-Chemist and Bio-physicist who spent his life in Academia and The Pharmaceutical Industry researching cures and treatments for diseases such as HIV/Aids, Diabetes, and Rheumatoid arthritis. His daughter sara inspires this blog and helps to write posts. sara was diagnosed with type 1 diabetes on april 4th, 2014 at the age of 30. 

2015 Update on Clinical Trial with Stem Cell Educator Therapy for Type 1 Diabetes

My blog is for information purposes only and should not be taken to make medical or other decisions. I'd like to thank my family and friends for helping me keep up to date with diabetes research.

Stem Cell Educator (SCE) Therapy is a medical procedure based on technology developed by Dr. Yong Zhao (now at Hackensack Medical University) and his collaborators. It uses multipotent stem cells from donors’ human umbilical cord blood (CB-SCs) to re-educate lymphocytes that have gone awry, to behave normally. Lymphocytes are a subtype of white blood cells fundamental to immune functions and in immune diseases, such as Type 1 Diabetes, that have lost their proper functions. SCE Therapy is briefly described at the end of this narrative.  Clinical trials (ClinicalTrials.gov number, NCT01350219) on Type 1 Diabetes based on SCE Therapy are ongoing and some of the results have been published in two papers.

 

In an earlier paper by Zhao et al. Reversal of Type 1 Diabetes via islet beta-cell regeneration following immune modulation by cord blood-derived multi-potent stem cells; BMC Medicine (2012) 10:3,  Dr. Zhao and collaborators published their clinical studies carried out in China, (from October 2010 through January 2011) with 15 Chinese patients having established T1D, (mean duration of diabetes ranging from 2-15 years). Six patients had residual β-cells before receiving a single SEC therapy treatment, and six had no residual β-cells prior to receiving a single SEC therapy treatment. The remaining three patients, who had residual β-cells, received sham therapy (sham therapy is a placebo). In an earlier blog post, I have already commented about the truly impressive results the investigators obtained.

Specifically, the study demonstrated:

The safety and therapeutic efficacy of Stem Cell Educator therapy in T1D patients;

Co-culturing patient lymphocytes with human umbilical cord blood CB-SC’s reversed autoimmunity; and

Regeneration of β-cells that led to better metabolic control (improved C-peptide levels, reduced A1C, and reduced the median dose of insulin) in all T1D patients except those who received sham therapy.

The second and most recent paper by Zhao and collaborators Delgado, E., et al., “Modulation of Autoimmune T-Cell Memory by Stem Cell Educator Therapy: Phase 1/2 Clinical Trial” EBioMedicine (2015), reported studies carried out in Spain with 15 Caucasian patients. Six patients had residual β-cells prior to treatment, while nine had no β-cells prior to treatment (in this case there were no sham therapy patients). The results are definitively less impressive than those reported with the Chinese patients.

Specifically the study demonstrated:

The safety of Stem Cell Educator therapy in T1D patients;

The ability to foster lasting reversal of autoimmune T-Cell memory in the treated patients; and

Some amelioration of C-peptide levels was also observed, but only in patients who still had functional β-cells at the beginning of the trial (not in those without any β-cells).

Unfortunately, no regeneration of β-cells, no reduction of hemoglobin A1C, and no median dose of insulin usage reduction were observed in the Caucasian patients. In my blog post on May 3, 2015, I reported a summary of an interview on March 6th, 2015 with Drs. Elías Delgado and Jesús Otero (two leaders of the Spanish trial) published by the Spanish newspaper, Asturias. In that interview, Dr. Delgado said that the Spanish study opened new questions about the differences between the pancreas of the Caucasian and the Chinese populations. Indeed, there are some genetic differences between the populations considered, which are now being studied to gain understanding. We hope that this will shed light on why the Spanish population had a different outcome than the Chinese population. In addition, Dr. Otero pointed out that the results cannot validate the technology with regard to a cure, given that the β-cells were not able to regenerate and that the patients still needed to inject insulin. Nevertheless, advancements were obtained in treating the disease in very young subjects whose cells still produced insulin. The two scientists expressed desire to continue their studies with the very young population. Now, after this publication with the Caucasian adult patients, I would like to see the published results of the Spanish study with the very young patients to see the advancement SCE therapy has accomplished.

 

Even though I am disappointed with the failed attempt of regenerating β-cells that produce endogenous insulin (endogenous means produced by the body), I believe that re-education of the immune system to proper functioning is of great importance. The question remains, how robust and long-lasting is the immune system re-education obtained from SCE therapy? Specifically, in terms of resetting the immune system of a diabetic to recognize his/her β-cells as non-foreigners and therefore as cells that must not be attacked and destroyed. Restoration of normal immune functions in a person with Type 1 Diabetes would open new avenues for curing this disease. I can see various possible applications and opportunities. For example, back in June 2015, Perle Bioscience, Inc., announced the recruitment of newly diagnosed T1D people for Phase III clinical trials (the last Phase prior to drug approval) with a combination of two compounds that are already individually approved by the Federal Drug Administration (FDA) for other medical applications. Interestingly, one compound is an over-the-counter antacid drug and, in the Perle Bioscience’s trial is for the regeneration of human β-cells. The other compound is a powerful immune suppressant, widely used to prevent organ transplant rejection; in the Perle Bioscience’s trial it is intended to prevent the immune system to attack the pancreatic β-cells. Immune suppressants are well-known to bring serious side effects, which constitutes a major drawback. Joshua Levy has recently written an interesting blog on these clinical trials.

 

Stem cell technology applications have been able to produce large quantities of β-cells (referred to as induced pluripotent stem cells, or iPSC) by reprogramming human cells (Pagliuca FW, Millman JR, Gurtler M, Segel M, Van Dervort A, et al. (2014) “Generation of Functional Human Pancreatic beta Cells In Vitro” Cell 159: 428–439 and Rezania A, Bruin JE, Arora P, Rubin A, Batushansky I, et al. (2014) “Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells” Nat Biotechnol 32: 1121–1133).

This is a progressive technology which could work in tandem with the SCE Therapy. Stem cell technology is expected to produce autologous β-cells (autologous means “engineered from that person’s own skin or other organ”), which could be suitable for safe implantation in that patient. The fact remains that this approach would require immune-suppressants to avoid β-cells being killed by a malfunctioning immune system.  On the other hand, a properly re-educated immune system (by SCE or another technology) would not require immune suppressants.

A brief description of the Stem Cell Educator (SCE) Therapy

It is taken by Zhao et al. Reversal of Type 1 Diabetes via islet beta-cell regeneration following immune modulation by cord blood-derived multi-potent stem cells; BMC Medicine (2012) 10:3

Figure 1. Overview of Stem Cell Educator therapy. A T1D participant (left) is connected to a Blood Cell Separator (right) and the Stem Cell Educator (bottom center) to form a closed system. Lymphocytes isolated from the T1D participant by the Blood Cell Separator travel through the Stem Cell Educator where they come in contact with CB-SCs attached to the interior surfaces of the device. Educated lymphocytes are returned to the patient's blood circulation. CB-SCs, cord blood stem cells; T1D, type 1 diabetes. 

2015 Type 1 Diabetes: Research Advances to develop a cure

2015 Artificial Pancreas: an interesting publication