Hypothesis: control autoimmune responses by altering regulatory T cells (Tregs) and human islet beta cell-specific T cell clones.
假設: 通過改變調節性T細胞(Treg細胞)和人體胰島β細胞特異性 T細胞克隆控制自身免疫反應”
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Method: "Stem Cell Educator therapy": the diabetic patient's blood is circulated through a closed-loop system that separates lymphocytes (a class of immune cell that includes T cells) from the whole blood and co-cultures them with cord blood stem cells from healthy donors for two to three hours before returning the "re-educated lymphocytes" to the patient's circulation.
方法：“幹細胞教育療法”: 糖尿病患者的血液通過一個閉環系統, 分離血液中的淋巴細胞至臍帶血造血幹細胞的裝置, 培養兩到三個小時進行 “再教育淋巴細胞", 然後再回至病人身體 。
Method: "Stem Cell Educator therapy": the diabetic patient's blood is circulated through a closed-loop system that separates lymphocytes (a class of immune cell that includes T cells) from the whole blood and co-cultures them with cord blood stem cells from healthy donors for two to three hours before returning the "re-educated lymphocytes" to the patient's circulation.
方法：“幹細胞教育療法”: 糖尿病患者的血液通過一個閉環系統, 分離血液中的淋巴細胞至臍帶血造血幹細胞的裝置, 培養兩到三個小時進行 “再教育淋巴細胞", 然後再回至病人身體 。
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Results: the median daily dose of required insulin was down by 38% at week 12 for the six patients with moderate diabetes and by 25% for the patients with severe diabetes. There was no change in required insulin dose for the controls.
All the patients who had received the Stem Cell Educator therapy also showed improved levels of C-peptide, a biomarker used to measure how well beta cells are working (it is a protein fragment that is left behind when insulin is made in the pancreas).
結果: 實驗組中度和嚴重糖尿病每日所需胰島素劑量中位數下降分別38％和25％, 對照組所需的胰島素劑量沒有變化.
實驗組患者的C肽生物標誌水平也有相對提高.
Results: the median daily dose of required insulin was down by 38% at week 12 for the six patients with moderate diabetes and by 25% for the patients with severe diabetes. There was no change in required insulin dose for the controls.
All the patients who had received the Stem Cell Educator therapy also showed improved levels of C-peptide, a biomarker used to measure how well beta cells are working (it is a protein fragment that is left behind when insulin is made in the pancreas).
結果: 實驗組中度和嚴重糖尿病每日所需胰島素劑量中位數下降分別38％和25％, 對照組所需的胰島素劑量沒有變化.
實驗組患者的C肽生物標誌水平也有相對提高.
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Clinical Study: Phase 1 / Phase 2 Study (15 patients), University of Illinois
臨床試驗: 階段1/ 階段2 研究(15名病人), 美國伊利諾伊大學
-------------------http://www.ncbi.nlm.nih.gov/pubmed?term=Reversal%20of%20type%201%20diabetes%20via%20islet%20%CE%B2%20cell%20regenerationfollowing%20immune%20modulation%20by%20cord%20blood-derivedmultipotent%20stem%20cells%20pubmed
Clinical Study: Phase 1 / Phase 2 Study (15 patients), University of Illinois
臨床試驗: 階段1/ 階段2 研究(15名病人), 美國伊利諾伊大學
-------------------http://www.ncbi.nlm.nih.gov/pubmed?term=Reversal%20of%20type%201%20diabetes%20via%20islet%20%CE%B2%20cell%20regenerationfollowing%20immune%20modulation%20by%20cord%20blood-derivedmultipotent%20stem%20cells%20pubmed
BMC Med. 2012 Jan 10;10(1):3. [Epub ahead of print]
Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells.
Zhao Y, Jiang Z, Zhao T, Ye M, Hu C, Yin Z, Li H, Zhang Y, Diao Y, Li Y, Chen Y, Sun X, Fisk MB, Skidgel R, Holterman M, Prabhakar B, Mazzone T.
Abstract
ABSTRACT:
BACKGROUND:
Inability to control autoimmunity is the primary barrier to developing a cure for type 1 diabetes (T1D). Evidence that human cord blood-derived multipotent stem cells (CB-SCs) can control autoimmune responses by altering regulatory T cells (Tregs) and human islet beta cell-specific T cell clones offers promise for a new approach to overcome the autoimmunity underlying T1D.
METHODS:
We developed a procedure for Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separate lymphocytes from the whole blood and briefly co-cultures them with adherent CB-SCs before returning them to the patient's circulation. In an open-label, phase1/phase 2 study, patients (n = 15) with T1D received one treatment with the Stem Cell Educator. Median age was 29 years (range, 15 to 41), and median diabetic history was 8 years (range, 1 to 21).
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 beta cell function (n = 6) and patients with no residual pancreatic islet beta 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 beta 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.
Trial registration: ClinicalTrials.gov number, NCT01350219.
- PMID:
- 22233865
- [PubMed - as supplied by publisher]
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