Clinical Applications

1. Stem Cell Educator therapy in type 1 diabetes (T1D)

In an open-label, phase1/phase 2 study, 15 patients with T1D received one treatment with the Stem Cell Educator.  Their median age was 29 years (range, 15 to 41), and median diabetic history was 8 years (range, 1 to 21). (ClinicalTrials.gov number, NCT01350219).

Results: Stem Cell Educator therapy was well tolerated in all participants with minimal pain from two venipunctures and no adverse events. Stem Cell Educator therapy can markedly improve C-peptide levels, reduce the median glycated hemoglobin A1C (HbA1C) values, and decrease the median daily dose of insulin in patients with some residual b cell function (n = 6) and patients with no residual pancreatic islet b cell function (n = 6). Treatment also produced an increase in basal and glucose-stimulated C-peptide levels through 40 weeks. However, participants in the Control Group (n = 3) did not exhibit significant change at any follow-up. Individuals who received Stem Cell Educator therapy exhibited increased expression of costimulating molecules (specifically, CD28 and ICOS), increases in the number of CD4+CD25+Foxp3+ Tregs, and restoration of Th1/Th2/Th3 cytokine balance. 

Conclusions: Stem Cell Educator therapy is safe, and in individuals with moderate or severe T1D, a single treatment produces lasting improvement in metabolic control. Initial results indicate Stem Cell Educator therapy reverses autoimmunity and promotes regeneration of islet b cells. Successful immune modulation by CB-SCs and the resulting clinical improvement in patient status may have important implications for other autoimmune and inflammation-related diseases without the safety and ethical concerns associated with conventional stem cell-based approaches. Notably, a single treatment could improve islet b function that lasts a year (see following case reports). Thus, findings from these trials indicate that CB-SC-mediated reversal of autoimmunity results from modulation of the immune response in multiple immune cell types, thereby meeting the expectation that successful therapies will likely address different arms of the autoimmune response and balance the immune system through the systemic and local modulations [7,8].

Currently, we are performing an international multicenter Phase II clinical study to improve the efficacy of Educator therapy. For more information, please visit the

Stem Cell Educator Therapy in Type 1 Diabetes at the ClinicalTrial.gov.  
 

 2. Stem Cell Educator therapy in type 2 diabetes (T2D)

Background: The prevalence of type 2 diabetes (T2D) is increasing worldwide and creating a significant burden on health systems, highlighting the need for the development of innovative therapeutic approaches to overcome immune dysfunction, which is likely a key factor in the development of insulin resistance in T2D. It suggests that immune modulation may be a useful tool in treating the disease.

 Methods: In an open-label, phase1/phase 2 study, patients (N = 36) with long-standing T2D were divided into three groups (Group A, oral medications, n = 18; Group B, oral medications + insulin injections, n = 11; Group C having impaired b-cell function with oral medications + insulin injections, n = 7). All patients received one treatment with the Stem Cell Educator therapy in which a patient’s blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, briefly co-cultures them with adherent CB-SCs, and returns the educated autologous cells to the patient’s circulation.

 Results: Clinical findings indicate that T2D patients achieve improved metabolic control and reduced inflammation markers after receiving Stem Cell Educator therapy. Median HbA1C in Group A and B was significantly reduced from 8.61% ± 1.12 at baseline to 7.25% ± 0.58 at 12 weeks (p = 2.62E-06), and 7.33%  ± 1.02 at one year post treatment (p = 0.0002). Homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) demonstrated that insulin sensitivity was improved post treatment (Figure top) . Notably, the islet beta-cell function in Group C subjects was markedly recovered (Figure bottom), as demonstrated by the restoration of C-peptide levels. Mechanistic studies revealed that Stem Cell Educator therapy reverses immune dysfunctions through immune modulation on monocytes and balancing Th1/Th2/Th3 cytokine production.

 Conclusions: Clinical data from current phase 1/2 study demonstrate that Stem Cell Educator therapy is a safe approach that produces lasting improvement in metabolic control for individuals with moderate or severe T2D who receive a single treatment. In addition, this approach does not appear to have the safety and ethical concerns associated with conventional stem cell-based approaches.

 

 







3. Clinical Case Report—Type 1 Diabetes: 

Case #1: A T1D subject (female, 15-year old, 5-year diabetic duration) received one treatment with Stem Cell Educator therapy, with one-year follow-up. C-peptide response following a 75-g oral glucose tolerance test (OGTT) reveals a significant improvement of b-cell Function by Stem Cell Educator Therapy. The dashed red line indicates the lower limit for normal C-peptide levels in Chinese populations. To convert C-peptide value to nmol/L, multiply the ng/ml by 0.331.

 

Case #2: C-peptide response following a 75-g OGTT from another severe T1D subject (male, 40-year old, 17-year diabetic duration) received one treatment with Stem Cell Educator therapy, with one-year follow-up. The level of 0.01 ng/ml is the minimum detectable level (sensitivity, the dashed purple line) of C-peptide by radioimmunoassay (RIA). To convert C-peptide value to nmol/L, multiply the ng/ml by 0.331.



 4. Clinical Case Report—Type 2 Diabetes:

Case#1: Before receiving the Stem Cell Educator therapy, patient A (male, 52 years old, 12 years diabetic duration) have been treated with current medications (e.g., metformin, sulfonylureas, pioglitazone), but failed to control his blood sugar levels (retaining at ~10 mmol/L), even though the insulin dose was increased to 70 U/day. He has been hospitalized with minor stroke (left brain). This patient displayed the typical insulin resistance, as demonstrated by a 75-g OGTT test with normal levels of fasting and stimulated C-peptide. After receiving the Stem Cell Educator therapy, his insulin dose was decreased by 20 U/day one month later, continually decreased to 50% on 6th month, with occurrence of hypoglycemia if injected a little bit more insulin. Notably, his HbA1C level was reduced from base line 9.4% to 7.1% on 6th month (note: 7% is the ADA-recommending standard for diabetics). His fasting blood sugar levels retained at 6 ~ 7 mmol/L. These data demonstrate that Stem Cell Educator therapy can markedly improve the insulin sensitivity and overcome the insulin resistance (the key issue of type 2 diabetes).

Case #2 : A long-standing diabetic patient B (female, 57 years old, 27 years diabetic duration, 32 U insulin/day) displayed an impaired islet beta cell function with the fasting C-peptide level 0.16 ng/ml (note: o.6 ng/ml is the lower limit for normal C-peptide levels in Chinese populations.). After receiving the Stem Cell Educator therapy for 3 months, her fasting C-peptide level was markedly increased to 0.54 ng/ml; correspondingly, her daily insulin dose was decreased by 50%. Her HbA1C level was reduced from base line 7.3 % to 6.4% on 3rd month. The data indicate that the Stem Cell Educator therapy can restore the islet beta cell function and improve the metabolic control.