Myoblasts

Chinn J A, Horbett T A, Ratner B D, Sohway M B, Hague Y and Hausohka S D 1989 Enhanoement of serum fibroneotin adsorption and the olonal plating of swiss mouse-3T3 fibroplast and MM14-mouse myoblast sells on polymer substrates modified by radiofrequenoy plasma deposition J. Colloid Interface Sol. 127 67-87... 

Muscle tissue is unique in its ability to shorten or contract. The human body has three basic types of muscle tissue histologically classified into smooth, striated, and cardiac muscle tissues. Only the striated muscle tissue is found in all skeletal muscles. The type of cells which compose the muscle tissue are known as contractile cells. They originate from mesenchymal cells which differentiate into myoblasts. Myoblasts are embryonic cells which later differentiate into contractile fiber cells. 

Skeletal muscle is made up of many muscle fibers (Figure 1) each of which is a multinucleated cell that was formed during development by the fusion of many cells (myoblasts). Skeletal muscle is formed from precursor myoblasts which arise... 

Figure 1. Muscle development. A skeletal muscle fiber is formed by the fusion of many single cells (myoblasts) into a multinucleated myotube. Myotubes then develop into the muscle fiber (see text). Sarcomeres form in longitudinal structures called myofibrils. The repeating structure of the sarcomere contains interdigitating thick and thin filaments.

Skapek, S.X., Rhee, J., Spicer, D.B. and Lassar, A.B. (1995) Inhibition of myogenic differentiation in proliferating myoblasts by cyclin D1 dependent kinase. 

Main producer cells Bone marrow stromal cell Macrophages Fibroblasts Lymphocytes Myoblasts Osteoblasts Monocytes Fibroblasts Endothelial cells Macrophages T-lymphocytes Fibroblasts Endothelial cells... 

Several cell types, including keratinocytes, myoblasts and fibroblasts, have been studied in this regard. It has been shown, for example, that myoblasts, into which the factor IX gene and the growth hormone gene have been introduced, could express their protein products and secrete them into the circulation. 

The putative receptor for agrin is a RPTK known as muscle-specific kinase (MuSK). The extracellular domain of MuSK resembles that of the ROR family of RPTKs, while the kinase domain is similar to that of the Trk neurotrophic receptor (Fig. 24-6). MuSK is expressed at low concentrations in proliferating myoblasts and is induced... 

Cogan JG, Sun S, Stoflet ES, Schmidt LJ, Getz MJ, Strauch AR 1995 Plasticity of vascular smooth muscle alpha-actin gene transcription. Characterization of multiple, single-, and double-strand specific DNA-binding proteins in myoblasts and fibroblasts. J Biol Chem 270 11310-11321... 

To date, cellular and gene therapy products submitted to FDA have included clinical studies indicated for bone marrow marking, cancer, cystic fibrosis, AIDS, and inborn errors of metabolism and infectious diseases. Of the current active INDs approximately 78% have been sponsored by individual investigators or academic institutions and 22% have also been industry sponsored. In addition to the variety of clinical indications the cell types have also been varied. Examples include tumor infiltrating lymphocytes (TIL) and lymphocyte activated killer (LAK) cells, selected cells from bone marrow and peripheral blood lymphocytes, for example, stem cells, myoblasts, tumor cells and encapsulated cells (e.g., islet cells and adrenal chromaffin cells). 

Duan, D., Z. Yan, Y. Yue, W. Ding, and J. F. Engelhardt. 2001. Enhancement of muscle gene delivery with pseudotyped adeno-associated virus type 5 correlates with myoblast differentiation. J Virol 75(16) 7662—71. 

Skeletal muscle is under conscious control. Each fibre is an enormous, multi-nucleate cell, formed by fusing hundreds of myoblasts end-to-end. They show a striated pattern, reflecting the regular arrangement of sarcomeres within each cell. 

Interestingly, highly elevated CSF-1 mRNA levels were also found in some of the non-secreting mutants (e.g. 4i-2, 51-2) (Fig. 9). In these mutants, CSF-1 may be acting internally within the CSF-1 receptor expressing cells as previously shown in rat myoblasts (Borycki et al., 1995). This specific form of... 

CSF-1 is synthesized by many different cell types including fibroblasts, endothelial cells, bone marrow stromal cells, osteoblasts, keratinocytes, astrocytes, myoblasts and, during pregnancy, under the control of estrogen and progesterone, by uterine epithelial cells. Circulating CSF-1 (ti/2 = 10 min) is synthesized by endothelial cells and smooth muscle cells. It is primarily cleared by CSF-lR-mediated internalization and destruction by Kupffer cells. Thus the number of sinusoidally located macrophages actually determines the concentration of the cytokine... 

Differentiated fibres are not capable of proliferation, but a small population of myoblasts (satellite cells) persists in mature muscle. They can be stimulated to proliferate and fuse with existing fibres to increase the number of nuclei present and restore the critical ratio of nuclei to cytoplasm that has been reduced by fibre enlargement. 

Contrasting with rodents, BAT is found in small amounts in adult humans. It has been proposed that skeletal muscle rather than BAT may play a pivotal role in energy homeostasis in adult humans. The authors also demonstrated that cultured human skeletal muscle myoblasts express D2 and high levels of TGR5, and a number of common bile acids (cholic acid, taurocholic acid, deoxycholic acid, chenodeoxycholic acid) were able to increase cAMP levels concomitant with increased D2 activity (Figure 7.4). Taurocholic acid was also able to... 

Skeletal myoblasts are adult, tissue-specific stem cells [73] located between the basal lamina and the sarcolemma on the periphery of the mature skeletal-muscle fiber [74]. Also known as muscle satellite cells, these small, mononuclear cells are activated by biochemical signals to divide and differentiate into fusion-competent cells after muscle injury. 

The use of skeletal myoblasts for cardiac repair originated from earlier attempts where fetal cardio-myocytes were used. When injected into the border... 

Skeletal myoblasts are viewed as an attractive alternative by some [76]. The first therapeutic trials used skeletal myoblasts obtained under sterile conditions and local anesthesia from 0.5- to 5.0-g muscle biopsy specimens. Individual cells were isolated by digestion with trypsin and collagenase, washed to remove red blood cells and debris, plated, and cultured to obtain the numbers necessary for therapeutic use. 

Skeletal myoblasts can survive prolonged periods of hypoxia [77]. Like fetal cardiomyocytes, skeletal myoblasts survive and may engraft (although this is controversial) when injected into the border zone of an AMI. 

Transcoronary venous injection is performed with a catheter system threaded percutaneously into the coronary sinus. Initial studies in swine have confirmed the feasibility and safety of this approach [121]. This delivery method has also been used to deliver skeletal myoblasts to scarred myocardium in cardiomyopathy patients [120]. With intravascular ultrasound guidance, this approach allows the operator to extend a catheter and needle away from the pericardial space and coronary artery into the adjacent myocardium. To date, human feasibility studies have had a good safety profile. This technique is limited, however, by coronary venous tortuosity, lack of site specific targeting, and its own technically challenging nature. Unlike the transendocardial approach, in which cells are... 

Clinical research with bone marrow-derived stem cells has focused on the period immediately after an AMI and on the chronic phase of ischemic heart disease. In these clinical scenarios, therapy has been targeted to viable myocardium with or without systolic heart failure. On the other hand, skeletal myoblast therapy has been used to treat ischemic heart failure involving nonviable myocardium or scar... 

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