Preclinical Study of Cell Therapy for Osteonecrosis of the Femoral Head with Allogenic Peripheral Blood-Derived Mesenchymal Stem Cells

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

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Innovative Cell Therapy in the Treatment of Serious Adverse Events Related to Both Chemo-Radiotherapy Protocol and Acute Myeloid Leukemia Syndrome: The Infusion of Mesenchymal Stem Cells Post-Treatment Reduces Hematopoietic Toxicity and Promotes Hematopoietic Reconstitution

Current Pharmaceutical Biotechnology ◽

10.2174/1389201014666131227120222 ◽

2014 ◽

Vol 14 (9) ◽

pp. 842-848 ◽

Cited By ~ 10

Author(s):

Loic Fouillard ◽

Sabine Francois ◽

Sandrine Bouchet ◽

Morad Bensidhoum ◽

Abdelatif Elm’selmi ◽

...

Keyword(s):

Stem Cells ◽

Acute Myeloid Leukemia ◽

Mesenchymal Stem Cells ◽

Adverse Events ◽

Cell Therapy ◽

Myeloid Leukemia ◽

Serious Adverse Events ◽

Hematopoietic Reconstitution ◽

Hematopoietic Toxicity ◽

Acute Myeloid

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Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02110-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Pegah Nammian ◽

Seyedeh-Leili Asadi-Yousefabad ◽

Sajad Daneshi ◽

Mohammad Hasan Sheikhha ◽

Seyed Mohammad Bagher Tabei ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Cell Therapy ◽

Femoral Artery ◽

Critical Limb Ischemia ◽

Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

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Mesenchymal stem cells: a new trend for cell therapy

Acta Pharmacologica Sinica ◽

10.1038/aps.2013.50 ◽

2013 ◽

Vol 34 (6) ◽

pp. 747-754 ◽

Cited By ~ 465

Author(s):

Xin Wei ◽

Xue Yang ◽

Zhi-peng Han ◽

Fang-fang Qu ◽

Li Shao ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Therapy

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Mesenchymal stem cells: Stem cell therapy perspectives for type 1 diabetes

Diabetes & Metabolism ◽

10.1016/j.diabet.2008.10.003 ◽

2009 ◽

Vol 35 (2) ◽

pp. 85-93 ◽

Cited By ~ 89

Author(s):

L. Vija ◽

D. Farge ◽

J.-F. Gautier ◽

P. Vexiau ◽

C. Dumitrache ◽

...

Keyword(s):

Stem Cells ◽

Type 1 Diabetes ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Cell Therapy ◽

Stem Cell Therapy

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Tissue-engineered Approach for the Treatment of Steroid-induced Osteonecrosis of the Femoral Head: Transplantation of Autologous Mesenchymal Stem Cells Cultured With Beta-Tricalcium Phosphate Ceramics and Free Vascularized Fibula

Artificial Organs ◽

10.1111/j.1525-1594.2006.00333.x ◽

2006 ◽

Vol 30 (12) ◽

pp. 960-962 ◽

Cited By ~ 113

Author(s):

Kenji Kawate ◽

Hiroshi Yajima ◽

Hajime Ohgushi ◽

Noriko Kotobuki ◽

Kazuya Sugimoto ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Femoral Head ◽

Tricalcium Phosphate ◽

Beta Tricalcium Phosphate ◽

Vascularized Fibula ◽

Autologous Mesenchymal Stem Cells ◽

Head Transplantation ◽

Cells Cultured

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Induction of Neurotrophin Expression via Human Adult Mesenchymal Stem Cells: Implication for Cell Therapy in Neurodegenerative Diseases

Cell Transplantation ◽

10.3727/000000007783464443 ◽

2007 ◽

Vol 16 (1) ◽

pp. 41-55 ◽

Cited By ~ 74

Author(s):

Federica Pisati ◽

Patrizia Bossolasco ◽

Mirella Meregalli ◽

Lidia Cova ◽

Marzia Belicchi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Therapy ◽

Neurodegenerative Diseases ◽

Human Adult ◽

Adult Mesenchymal Stem Cells

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Abstract MP243: Detection Of Mesenchymal Stem Cells In Mobilized Autologous Peripheral Blood Transplantation From Patients With Ischemic Heart Disease

Circulation Research ◽

10.1161/res.129.suppl_1.mp243 ◽

2021 ◽

Vol 129 (Suppl_1) ◽

Author(s):

Hadyanto Lim ◽

Umar Zein ◽

Ilham Hariaji

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Heart Disease ◽

Ischemic Heart Disease ◽

Peripheral Blood ◽

Autologous Transplantation ◽

White Blood Cells ◽

Significant Rise ◽

Ischemic Heart ◽

Post Transplantation

Background: Mesenchymal stem cells (MSCs) improve the cardiac function and remodeling in patients with ischemic heart disease. However, their presence in the circulating peripheral blood and post-transplantation has not been fully elucidated. We aimed to investigate the effects of intravenous transplantation of mobilized autologous peripheral blood on the number of MSCs in patients with ischemic heart disease. Methods: Granulocyte-colony stimulating factor (G-CSF, 5.0 μg/kg/day) was given subcutaneously once a day for five days to 7 patients (4 women and 3 men, aged 54-69 years) with ischemic heart disease. Leukapheresis procedure was started on the day 5 of G-CSF using the Spectra Optia cell separator. Circulating and intravenous transplantation of autologous MSCs after leukapheresis were analyzed by flow cytometry. MSCs were identified on the basis of dual positive cells (CD73 + /CD105 + or CD90 + /CD73 + or CD90 + /CD105 + ) and detected as MSCs if a cluster of at least 10 cells could be found. Results: MSCs in the circulating peripheral blood and after transplantation were detected in 2 (28%) and 6 (85%) patients, respectively. The frequency of intravenous peripheral blood MSCs increased significantly after transplantation (from 32.57 ± 22.76 x10 -4 % to 58.57 ± 28.49 x 10 -4 % , p<0.001). Moreover, there were significant rise in the total white blood cells count (from 10.25 ± 4.86 x 10 3 /μl to 35.81 ± 7.07 x 10 3 /μl, p<0.001) and the levels of CD34 + cells (from 1.17 ± 0.93 cells/μL to 138.30 ± 11.26 cells/μL, p<0.001) after the infusion. Conclusions: The results show that intravenous transplantation of mobilized autologous peripheral blood increases the number of MSCs in patients with ischemic heart disease. Leukapheresis product of peripheral blood MSCs could therefore be a potential source for autologous transplantation in ischemic heart disease.

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