Autologous Bone Marrow Derived Mesenchymal Stromal Cells Transplantation for Human Avascular Necrosis of the Lunate Bone of the Wrist (Kienbock's Disease)

Kienböck's disease is characterized by avascular necrosis of the lunate wrist bone, which is usually progressive without treatment.
Cell therapy is useful in treatment of degenerated bone and mesenchymal stromal/stem cells are the best candidates for this kind of treatment.
This study examined lunate core decompression in combination with implantation of autologous bone marrow derived mesenchymal stromal cells for Its treatment potential.
Bone decompression in combination with implantation of autologous bone marrow derived mesenchymal stromal/stem cell will be done in 30 patients with Kienböck disease.
The patients will be followed at 2weeks, 3months, 6m and 12 months after implantation.
The Spss(v16) software will be used for data analysis.

开始日期2015-11-01

申办/合作机构

Royan Institute

NCT04078308 / Unknown status临床1/2期IIT

Phase I/II Clinical Trial to Examine the Safety and Efficacy of Transplantation of Mesenchymal Stem Cells in New-onset Type 1 Diabetes Patients

Study Objects: Diabetes is an autoimmune disease which is mainly caused an immune reaction to beta cells in the pancreas. In this study, mesenchymal stem cells will be used for immune response modulation and improving regeneration. Study design and method: In a Triple blinded randomized placebo-controlled phase I/II clinical trial, 20 patients with newly diagnosed type-1 diabetes who would be visited in Children's Growth and Development Research Center of Tehran University of Medical Sciences and Royan Institute Cell Therapy Center, would be assessed through two groups including the case group and the placebo group. Participants: Patients of both sexes in a range of 8 to 40 years old who have been diagnosed to have type-1 diabetes in no more than 6 weeks, antibody against beta cells diagnosed in their blood, fasting c-peptide more than or equal to 0.3 ng/ml, and are not suffered from other acute or chronic diseases and cancers, would be studied. Interventions: Intravascular transplantation of autologous mesenchymal stem cells in the case group; placebo injection in the control group. Outcome variables: safety and efficacy.

开始日期2015-07-06

申办/合作机构

Royan Institute

[+1]

NCT02195323 / Completed临床1期IIT

Administration of Autologous Bone Marrow Mesenchymal Stem Cells (BM-MSCs) in Patients With Chronic Kidney Disease (CKD)

This study was designed to provide confirmation of safety of mesenchymal stem cells (MSCs) therapy in chronic kidney disease (CKD).

开始日期2014-04-01

申办/合作机构

Royan Institute

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项与 AC-133(Royan Institute) 相关的文献（医药）

2019-09-01·The Quarterly Journal of Nuclear Medicine and Molecular Imaging4区 · 医学

SPECT imaging of colorectal cancer by targeting CD 133 receptor with 99mTc-labeled monoclonal antibody

4区 · 医学

Article

作者: Jin, Xueyan ; Lang, Juntao ; Lan, Xiaoli ; Liu, Yu ; Wen, Qiong ; An, Rui

BACKGROUNDPrevious reports suggested that CD133-positive cells had biological features of cancer stem cells (CSCs). Furthermore, CD133 expression was reported as an unfavorable prognostic factor in patients. Therefore, a new radiolabeled probe, 99mTc labeled AC133 antibody which binding with CD133 specifically, was developed to noninvasively detect CSCs by SPECT in vivo.METHODSCD133 expression was evaluated by flow cytometry in three colon cancer cell lines (HCT116, Lovo and DLD1). AC133 antibody and control IgG were conjugated with succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH), and then labeled with 99mTc. The new radiolabeled probe was named as 99mTc-SHNH-AC133. The vitro cell binding assays, series SPECT imaging and biodistribution analyses were performed. Flow cytometry, immunofluorescence staining of tumor tissues were carried to verify the in-vivo imaging results.RESULTS99mTc-SHNH-AC133 was labeled with a high radiochemical purity (97.7±2.4%, N.=3) and specific activity (4.07 MBq/µg). Cellular experiments showed that the labeled AC133 antibody retained with a high binding affinity on CD133-positive cells (HCT116 and Lovo cells). Biodistribution analyses showed high tumor uptake of the tracer in HCT116 and Lovo xenografts (8.82±0.73 and 7.37±0.26 %ID/g, respectively, N.=4) and high tumor-to-muscle ratios (13.18±2.84 and 11.13±0.53, respectively, N.=4) at 36 h after injection, resulting in high contrast SPECT images with high specific tumor uptake. However, the tumor bearing CD133-negative cell (DLD1 cells) showed no obvious uptake of 99mTc-SHNH-AC133 both in-vitro cell binding and in-vivo imaging study. Moreover, the tumor uptake of 99mTc-SHNH-AC133 in positive tumor models was significantly reduced by pre-injection of excess unlabeled AC133 antibody. Flow cytometric analysis and immunofluorescence staining confirmed the CD133 expression in tumors, which correlated well with the in-vivo results.CONCLUSIONSThis study showed that 99mTc-SHNH-AC133 exhibited high uptake in CD133-positive tumors. The high specificity and good tumor targeting properties of 99mTc-SHNH-AC133 may provide a new method to track or locate CSCs.

2016-01-01·Theranostics1区 · 医学

Imaging and Selective Elimination of Glioblastoma Stem Cells with Theranostic Near-Infrared-Labeled CD133-Specific Antibodies

1区 · 医学

ArticleOA

作者: Jing, Hua ; Weidensteiner, Claudia ; Reichardt, Wilfried ; Grosu, Anca-Ligia ; Gaedicke, Simone ; Niedermann, Gabriele ; Zhu, Xuekai ; Kobayashi, Hisataka

Near-infrared photoimmunotherapy (NIR-PIT), which employs monoclonal antibody (mAb)-phototoxic phthalocyanine dye IR700 conjugates, permits the specific, image-guided and spatiotemporally controlled elimination of tumor cells. Here, we report the highly efficient NIR-PIT of human tumor xenografts initiated from patient-derived cancer stem cells (CSCs). Using glioblastoma stem cells (GBM-SCs) expressing the prototypic CSC marker AC133/CD133, we also demonstrate here for the first time that NIR-PIT is highly effective against brain tumors. The intravenously injected theranostic AC133 mAb conjugate enabled the non-invasive detection of orthotopic gliomas by NIR fluorescence imaging, and reached AC133+ GBM-SCs at the invasive tumor front. AC133-targeted NIR-PIT induced the rapid cell death of AC133+ GBM-SCs and thereby strong shrinkage of both subcutaneous and invasively growing brain tumors. A single round of NIR-PIT extended the overall survival of mice with established orthotopic gliomas by more than a factor of two, even though the harmless NIR light was applied through the intact skull. Humanised versions of this theranostic agent may facilitate intraoperative imaging and histopathological evaluation of tumor borders and enable the highly specific and efficient eradication of CSCs.

2015-11-01·Leukemia1区 · 医学

Control of AC133/CD133 and impact on human hematopoietic progenitor cells through nucleolin

1区 · 医学

Article

作者: Grinstein, E ; Meisel, R ; Bhatia, S ; Reister, S ; Borkhardt, A ; Mahotka, C

AC133 is a prominent surface marker of CD34+ and CD34- hematopoietic stem/progenitor cell (HSPC) subsets. AC133+ HSPCs contain high progenitor cell activity and are capable of hematopoietic reconstitution. Furthermore, AC133 is used for prospective isolation of tumor-initiating cells in several hematological malignancies. Nucleolin is a multifunctional factor of growing and cancer cells, which is aberrantly active in certain hematological neoplasms, and serves as a candidate molecular target for cancer therapy. Nucleolin is involved in gene transcription and RNA metabolism and is prevalently expressed in HSPCs, as opposed to differentiated hematopoietic tissue. The present study dissects nucleolin-mediated activation of surface AC133 and its cognate gene CD133, via specific interaction of nucleolin with the tissue-dependent CD133 promoter P1, as a mechanism that crucially contributes to AC133 expression in CD34+ HSPCs. In mobilized peripheral blood (MPB)-derived HSPCs, nucleolin elevates colony-forming unit (CFU) frequencies and enriches granulocyte-macrophage CFUs. Furthermore, nucleolin amplifies long-term culture-initiating cells and also promotes long-term, cytokine-dependent maintenance of hematopoietic progenitor cells. Active β-catenin, active Akt and Bcl-2 levels in MPB-derived HSPCs are nucleolin-dependent, and effects of nucleolin on these cells partially rely on β-catenin activity. The study provides new insights into molecular network relevant to stem/progenitor cells in normal and malignant hematopoiesis.

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