Background: Myoblast transplantation has long been studied as a potential therapy for Duchenne muscular dystrophy as the incorporation of donor myoblasts into host muscle allows the production of functional dystrophin protein. However, the clinical feasibility of this approach is limited by the poor survival of the donor cells in the weeks after transplantation. It has recently been determined that the intramuscular transplantation of large numbers of cells can lead to the formation of ischemic necrosis in the center of these cell masses. For this reason, the relationship between donor cell survival and the number of cells transplanted was investigated.
Methods: Myoblasts were prepared from the hind limb muscles of male C57BL/10Sn mice and transplanted into the tibialis anterior muscles of female mdx mice at one of the following amounts: 10, 10, 10, or 10 cells. The survival of the transplanted cells was analyzed using a Y chromosome-specific qPCR.
Results: It was found that donor cell survival was improved 1 week after transplantation when fewer myoblasts were transplanted, including the observation of donor cell proliferation after the transplantation of 10 myoblasts. However, concentration effects and long-term survival complicate the interpretation of these results.
Conclusions: These results indicate that early donor myoblast survival was dependent on the number of cells transplanted and the volume of liquid used to deliver them into the muscle. We believe that this finding has implications for the design and interpretation of future experimentation relating to intramuscular cell therapies.
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Sci Rep
December 2024
Laboratorio de Pesquisa em Cirurgia Toracica, Departamento de Cardiopneumologia, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Currently, the barrier to successful lung transplantation is ischemia and reperfusion injury, which can lead to the development of bronchiolitis obliterans. Paclitaxel and methotrexate are drugs known to inhibit cell proliferation and have anti-inflammatory effects, and the association of these drugs with cholesterol-rich nanoparticles has been shown to be beneficial in the treatment of other transplanted organs. Thirty-three male Sprague Dawley rats were divided into 3 groups: Basal group, no intervention; Control group, received only nanoparticles; Drug group, paclitaxel and methotrexate treatment.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4 T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL.
View Article and Find Full Text PDFOral Dis
December 2024
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Background: To meet their high energy needs, tumor cells undergo aberrant metabolic reprogramming. A tumor cell may expertly modify its metabolic pathways and the differential expression of the genes for metabolic enzymes. The physiological requirements of the host tissue and the tumor cell of origin mostly dictate metabolic adaptation.
View Article and Find Full Text PDFFEBS Lett
December 2024
Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Fluorescence resonance energy transfer (FRET)-based biosensors are powerful tools for studying second messengers with high temporal and spatial resolution. FRET is commonly detected by ratio imaging, but fluorescence lifetime imaging microscopy (FLIM), which measures the donor fluorophore's lifetime, offers a robust and more quantitative alternative. We have introduced and optimized four generations of FRET sensors for cAMP, based on the effector molecule Epac1, including variants for either ratio imaging or FLIM detection.
View Article and Find Full Text PDFArtif Organs
December 2024
Department of Mechanical Engineering, University of Washington, Seattle, Washington, USA.
Background: Liver disease is a growing burden. Transplant organs are scarce. Extracorporeal liver support systems (ELSS) are a bridge to transplantation for eligible patients.
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