Tuesday, November 27, 2012

Protein Injection Strategy

(Continuously Updating)

Paper 1: Wnt7a treatment ameliorates muscular dystrophy

Strategy :

  1.  Wnt7a treatment efficiently induced satellite cell expansion and myofiber hypertrophy in treated mucles in mdx mice.
    1. Wnt7a signaling through its receptor Fzd7 accelerates and augments regeneration by:
      1. stimulating satellite stem cell expansion through the planar cell polarity pathway, as well as,
      2. myofiber hypertrophy through the AKT/mammalian target of rapamycin (mTOR) anabolic pathway. 

Application:

  1. Duchenne muscular dystrophy (DMD)

References: 

  1. J. von Maltzahn, J.-M. Renaud, G. Parise, M. A. Rudnicki.Wnt7a treatment ameliorates muscular dystrophy.Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1215765109

Cells Rejuvenation Strategy

(Continuously Updating)

Paper 1: Aged human cells rejuvenated by cytokine enhancement of biomaterials for surgical ventricular restoration.

Strategy : 

  1.  cytokine enhancement of a biodegradable patch
    1.  covalently immobilized 2 proangiogenic cytokines (vascular endothelial growth factor and basic fibroblast growth factor) onto porous collagen scaffolds.
    2.  seeded human mesenchymal stromal cells from old donors into the scaffolds with  growth factors

Application: 

  1. Surgical ventricular restoration (SVR)


References:


  1. Kang KSun LXiao YLi SHWu JGuo JJiang SLYang LYau TMWeisel RDRadisic MLi RK. Aged human cells rejuvenated by cytokine enhancement of biomaterials for surgical ventricular restoration. J Am Coll Cardiol. 2012 Nov 20;60(21):2237-49. doi: 10.1016/j.jacc.2012.08.985. (Department of Cardiovascular Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China; Division of Cardiovascular Surgery and Toronto General Research Institute, University Health Network and Department of Surgery, Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada.) PMID: 23153846

Thursday, July 26, 2012

Animal trials of Mesoblast's (ASX:MSB) mesenchymal stem cells in rheumatoid arthritis (RA) have encouraged the company press on with an FDA application for a phase II trial.

Original article:
http://www.lifescientist.com.au/article/431662/mesoblast_eyes_human_trials_stem_cell_treatment_rheumatoid_arthritis/


Mesoblast (ASX:MSB) is continuing to expand the applications for its off-the-shelf stem cell technology by pushing forward to conduct a phase II trial for rheumatoid arthritis (RA).

This follows encouraging results from preclinical trials of its adult stem cells in animal models of RA.

The company revealed that a single injection of its mesenchymal precursor cells (MPCs) was able to simultaneously inhibit multiple cytokines responsible for driving RA.

The MPCs concomitantly affected T cells, monocytes and synoviocytes to shut down TNF-alpha, IL-6 and IL-I7 cytokine pathways in sheep with collagen-induced arthritis.

Treatments that shut down any of these pathways alone are only moderately effective at treating RA, and often need to be administered chronically.

Based on the promising results, Mesoblast has arranged a meeting with the US FDA to discuss organising a phase II trial.

Subject to receiving approval, the company plans to conduct a randomised, placebo-controlled phase II trial in the fourth quarter.

During the pilot study, significant numbers of allogenic MPCs were detected in involved joints or lymph nodes of the arthritic sheep, but not in normal sheep. This suggests the MPCs selectively migrate to sites of immune-mediated inflammation.

Sheep were injected with three different quantities of MPCs. Joint tissue from sheep receiving the largest dose showed an 88% mean reduction in IL-6 levels, an 83% reduction in TNF-alpha levels and a 52% reduction in IL-I7 levels.

MPC-treated animals had a 31% mean reduction in histopathology severity scores compared to the control group.

Sunday, February 12, 2012

Twenty autologous umbilical cord blood from private cord blood banks were evaluated for thaw characteristics. 研究對私人臍帶血庫的21個自體臍血進行解凍後的特點評估.


Twenty autologous umbilical cord blood from private cord blood banks were evaluated for thaw characteristics: "only 11% of evaluable autologous umbilical cord blood achieved the minimum total nucleated cell count of at least 9.0×10(8) to meet the National Cord Blood Inventory banking threshold and only 50% met the minimum of 5.0×10(8) TNC count for Food and Drug Administration cord blood licensure eligibility."

研究對私人臍帶血庫的21個自體臍血進行解凍後的特點評估“只有11%的自體臍血達到了9.0×10(8)的最低總核細胞數目, 以滿足國家臍帶血庫存的門檻; 此外, 亦只有50%的自體臍血達到了5.0×10(8)
總核細胞數目,以滿足食品和藥物管理局臍帶血執照資格.

------------------

Transfusion. 2012 Feb 10. doi: 10.1111/j.1537-2995.2011.03556.x. [Epub ahead of print]

Characteristics of thawed autologous umbilical cord blood.

Source

From the Department of Medicine, the Department of Pediatrics, and the Department of Epidemiology and Health Policy Research, University of Florida, and Shands Hospital at the University of Florida, Gainesville, Florida; and the Department of Pediatrics Patient Care, University of Texas MD Anderson Cancer Center, Houston, Texas.

Abstract

BACKGROUND:

Autologous umbilical cord blood (AutoUCB) has historically been cryopreserved for potential use in hematopoietic transplantation. Increasingly, private AutoUCB banking is performed for therapies unavailable today. A Phase I trial using AutoUCB treatment for early pediatric Type 1 diabetes afforded us an opportunity to analyze characteristics of AutoUCBs.

STUDY DESIGN AND METHODS:

Twenty AutoUCBs from AABB-accredited private cord blood banks (CBBs) were evaluated for collection, processing, cryopreservation, and thaw characteristics. Using a standardized thaw-wash method, AutoUCBs were assessed for viable total nucleated cells (vTNCs), viable CD34+ (vCD34+), and colony-forming unit-granulocyte-macrophage counts. Postthaw %vTNC recoveries were compared against processing characteristics and analyzed according to processing method, cryopreservation volume, concentration, container, and length of storage.

RESULTS:

AutoUCB collection volumes (19.9-170 mL), cryopreserved TNC counts (7.6× 10(7) -3.34×10(9) ), %TNC processing recoveries (39%-100%), postthaw %vTNC recoveries (58%-100%), and %vCD34+ recoveries (26%-96%) varied widely. Regarding cell dose requirements, only 11% of evaluable AutoUCBs achieved the minimum TNC count of at least 9.0×10(8) to meet the National Cord Blood Inventory banking threshold, and only 50% met the minimum of 5.0×10(8) TNC count for Food and Drug Administration cord blood licensure eligibility. %vTNC recoveries correlated with %vCD34+ recoveries (R=0.7; p=0.03). Length of storage, cryopreservation volume, concentration, and container type did not affect postthaw %vTNC recoveries. CBB processing method, however, was associated with %vTNC postprocessing recoveries, with unmanipulated and plasma-depleted AutoUCBs having the highest postthaw %vTNC recovery, followed by RBC-depleted and density gradient-separated AutoUCBs.

CONCLUSION:

The high variability and low counts found in AutoUCB banking suggest that further standardization of characterization, collection, and processing procedures is needed.
© 2012 American Association of Blood Banks.
PMID:
 
22321210
 
[PubMed - as supplied by publisher]

A pilot study shows Intrabone Cord Blood Hematopoietic Stem Cell Transplantation is safe and feasible in pediatrics. 一項初步研究顯示:移植臍血造血幹細胞至骨髓內在兒科是安全和可行的.


http://www.ncbi.nlm.nih.gov/pubmed/22322938

J Pediatr Hematol Oncol. 2012 Feb 8. [Epub ahead of print]

Intrabone Cord Blood Hematopoietic Stem Cell Transplantation in a Subset of Very High-Risk Pediatric Patients: A Safety and Feasibility Pilot Study.

Source

*Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division †Immunohematology and Transfusion Medicine Service, Regina Margherita Children's Hospital, Turin, Italy.

Abstract

The main limit of umbilical cord blood hematopoietic stem cell transplantation is a more difficult engraftment related to the number of cells infused per kilogram of recipient body weight. This limit makes the cord blood a suboptimal source of hematopoietic stem cells for transplantation in case of difficult engraftment situations. Direct intrabone cord blood (CB) injection has been recently investigated as a solution to cell dose problem in the adults population, but there is a lack of data concerning this approach in pediatric patients. Here, we describe 5 pediatric patients undergoing intrabone cord blood transplantation (IBCBT) for different diseases characterized by a high risk of posttransplant graft failure. The conditioning regimen differed according to the disease, whereas the GvHD prophylaxis consisted of cyclosporine, mycophenolate, and ATG. The median numbers of total nucleated cells infused and CD34 cells were 3.3×10/kg, 2×10/kg. All the patients showed complete hematological recovery and complete donor engraftment. No patient had secondary graft failure, whereas 1 patient relapsed 6 months after IBCBT. No patient died of transplant-related complications. Our results show that IBCBT is safe and feasible in pediatrics as well, and suggest that IBCBT might be an attractive option to overcome some limits of umbilical cord blood hematopoietic stem cell transplantation.
PMID:
 
22322938
 
[PubMed - as supplied by publisher]

Wednesday, February 1, 2012

Cord Blood "Stem Cell Educator therapy" may Reverse Type 1 Diabetes - Phase 1 / Phase 2 Clinical Study. 臍帶血“幹細胞教育療法”或逆轉1型糖尿病 (胰岛素依赖型糖尿病) - 階段1/ 階段2 臨床試驗.


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”

------------------
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 。
------------------
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.
-----------------
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


http://www.medicalnewstoday.com/articles/240160.php

----------------------------------

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.

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] 
Free full text








Tuesday, January 24, 2012

胚胎幹細胞注射到視網膜組織令兩名患嚴重眼疾的病人有顯著改善 (CNN: Embryonic stem cells improve vision for two women)

首次科學研究結果記載: 具有爭議性的胚胎幹細胞(Embryonic stem cells) 注射到視網膜組織令兩名患嚴重眼疾的病人有顯著改善. 研究人員強調, 這是初步結果 .


http://edition.cnn.com/2012/01/23/health/stem-cell-research-breakthrough/?hpt=hp_t2

Embryonic stem cells improve vision for two women

By Elizabeth Cohen, Senior Medical Correspondent
January 24, 2012 -- Updated 0321 GMT

Saturday, January 21, 2012

韩国批准销售新的干细胞的药物(法新社, 2012-01-20)


S. Korea approves sales of new stem cell drug
首尔- 韩国政府药品监督管理局周四宣布批准世界上第一个的从其他人收集的医药使用干细胞作商业销售.
SEOUL — South Korea's government drug agency cleared the way Thursday for commercial sales of what it called the world's first approved medicine using stem cells collected from other people.

韩国食品和药物管理局称: 汉城Medipost开发的Cartistem将使用从新生儿脐带血干细胞辅助再生膝盖软骨.
Cartistem, developed by Seoul-based Medipost, will help regenerate knee cartilage using stem cells developed from newborns' umbilical cord blood, the Korea Food and Drug Administration said.

“Cartistem是世界上第一个批准的异体(从同一物种的不同个体采取)干细胞的药物,它可以提供新的治疗机遇给退化性关节炎患者”,政府在一份声明中表示.
"Cartistem is... the world's first approved allogeneic (taken from different individuals of the same species) stem cell drug, that can offer new opportunity for treatment of patients with degenerative arthritis," the administration said in a statement.

Medipost称私人投资者和政府基金已自2001年以来投资270亿韩元($2380万美元)发展Cartistem. 此药物可以通过手术注射到患者的膝盖.
Medipost said 27 billion won ($23.8 million) from private investors and government funds had been invested to develop Cartistem since 2001. The drug can be injected into a patient's knees via surgery.

声明中称,自去年以来(药物)已经在美国进行临床试验.
Clinical trials have been under way in the United States since last year, the statement said.

Medipost发言人对法新社记者称, 两间世界排名前10位的制药公司正在谈判寻求全世界范围的药物许可使用权, 大规模的最终临床试验大可能会在2015年在美国开始.
Two of the world's top 10 drugmakers are in talks to seek a worldwide licence to make the drug, a Medipost spokesman told AFP, adding that final trials involving a large number of people would likely begin in the US in 2015.


免责声明: 以上中文翻译版本只供参考用途.
Disclaimer: The above Chinese translation version is for reference only.


Translated by Pat Chu on 2012-01-21

Friday, January 20, 2012

韓國批准銷售新的幹細胞的藥物 (法新社, 2012-01-20)

S. Korea approves sales of new stem cell drug

首爾 - 韓國政府藥品監督管理局週四宣布批准世界上第一個的從其他人收集的醫藥使用幹細胞作商業銷售。
SEOUL — South Korea's government drug agency cleared the way Thursday for commercial sales of what it called the world's first approved medicine using stem cells collected from other people.

韓國食品和藥物管理局稱: 漢城Medipost開發的Cartistem將使用從新生兒臍帶血幹細胞輔助再生膝蓋軟骨.
Cartistem, developed by Seoul-based Medipost, will help regenerate knee cartilage using stem cells developed from newborns' umbilical cord blood, the Korea Food and Drug Administration said.

“Cartistem是世界上第一個批准的異體(從同一物種的不同個體採取)幹細胞的藥物,它可以提供新的治療機遇給退化性關節炎患者”,政府在一份聲明中表示.

"Cartistem is... the world's first approved allogeneic (taken from different individuals of the same species) stem cell drug, that can offer new opportunity for treatment of patients with degenerative arthritis," the administration said in a statement.

Medipost稱私人投資者和政府基金已自2001年以來投資270億韓元($2380萬美元)發展 Cartistem. 此藥物可以通過手術注射到患者的膝蓋.

Medipost said 27 billion won ($23.8 million) from private investors and government funds had been invested to develop Cartistem since 2001. The drug can be injected into a patient's knees via surgery.

聲明中稱,自去年以來(藥物)已經在美國進行臨床試驗。
Clinical trials have been under way in the United States since last year, the statement said.

Medipost發言人法新社記者稱, 兩間世界排名前10位的製藥公司正在談判尋求世界範圍的藥物許可使用權, 大規模的最終臨床試驗大可能會在2015年在美國開始.
Two of the world's top 10 drugmakers are in talks to seek a worldwide licence to make the drug, a Medipost spokesman told AFP, adding that final trials involving a large number of people would likely begin in the US in 2015.


免責聲明:  以上中文翻譯版本只供參考用途.
Disclaimer: The above Chinese translation version is for reference only.



Translated by Pat Chu on 2012-01-21



Kalorama 研究報告今年的幹細胞技術的市場將上升到7億美元以上.




原文: http://www.healthcarefinancenews.com/news/stem-cell-technologies-market-hit-700m-2012


根據醫療保健市場研究出版商Kalorama資訊, 本年度幹細胞技術的市場將上升到7億美元以上,並具有趨勢可能達到 10億美元以上.


在其新報告中,“幹細胞移植,臍帶血和藥物開發的全球市場” Kalorama預測美國新允許使用幹細胞技術的情況和攜同的科研經費積極作用取決於多項因素。

Kalorama信息的發布者 Bruce Carlson 說:"一個十分可能的情況是, 開發商將繼續擴大倫理上比較容易接受的"成幹細胞"的運用,專利和特許權使用費不會嚴重財政問題。我們還預計,至少部分目前正在開發的技術將被證明是安全的,並顯示比較目前的療法有大的好處."


細胞療法現在主要限使用於腫瘤,如白血病(leukemia),多發性骨髓瘤(multiple myeloma )和非霍奇金淋巴瘤(non-Hodgkins lymphoma)將會越來越多使用於非癌疾病,如再生障礙性貧血(aplastic anemia),免疫缺陷 (immunodeficiency)和狼瘡 (lupus)等.


Kalorama發現,增加 臍帶血儲存也是收入增長的來源之一。臍血幹細胞爭議最少的幹細胞不需要未開發的技術, 所以很多人支持 出生時收集臍帶血的概念.


美國過去最強烈反對胚胎幹細胞研究的的國家,在2009年,奧巴馬政府發布行政命令13505,其中明確列明擴大國立衛生研究院 (NIH) 人類幹細胞研究的支持。因此,美國國立衛生研究院幹細胞研究經費從 2003年到2010年穩步增長,尤其是是在過去兩年.



免責聲明:  以上中文翻譯版本只供參考用途.
Disclaimer: The above Chinese translation version is for reference only.


Translated by Pat Chu on 2012-01-20





-------------------------------


Kalorama 研究报告: 今年的干细胞技术的市场将上升到7亿美元以上.

原文: http://www.healthcarefinancenews.com/news/stem-cell-technologies-market-hit-700m-2012

根据医疗保健市场研究出版商Kalorama资讯, 本年度干细胞技术的市场将上升到7亿美元以上,并具有趋势可能达到10亿美元以上.

在其新报告中,“干细胞移植,脐带血和药物开发的全球市场” Kalorama预测美国的新允许使用干细胞技术的情况和携同的科研经费有积极作用, 但取决于多项因素。

Kalorama信息的发布者Bruce Carlson 说:"一个十分可能的情况是, 开发商将继续扩大伦理上比较容易接受的"成人干细胞"的运用,专利和特许权使用费将不会是严重财政问题。我们还预计,至少部分目前正在开发的技术将被证明是安全的,并显示比较目前的疗法有更大的好处."

细胞疗法现在主要限使用于肿瘤,如白血病(leukemia),多发性骨髓瘤(multiple myeloma )和非霍奇金淋巴瘤(non-Hodgkins lymphoma); 但将会有越来越多使用于非癌疾病,如再生障碍性贫血(aplastic anemia),免疫缺陷(immunodeficiency)和狼疮(lupus)等.

Kalorama发现,增加脐带血储存也是收入增长的来源之一。脐血干细胞是争议最少的干细胞及不需要未开发的技术, 所以有很多人支持出生时收集脐带血的概念.

美国过去是最强烈反对胚胎干细胞研究的的国家,但在2009年,奥巴马政府发布行政命令13505,其中明确列明扩大国立卫生研究院(NIH) 对人类干细胞研究的支持。因此,美国国立卫生研究院干细胞研究经费从2003年到2010年都有稳步增长,尤其是是在过去两年.


免责声明: 以上中文翻译版本只供参考用途.
Disclaimer: The above Chinese translation version is for reference only.


Translated by Pat Chu on 2012-01-20