Connective Tissue Cells

Integrating cells into tissues

Susan Standring MBE, PhD, DSc, FKC, Hon FAS, Hon FRCS , in Gray's Anatomy , 2021

Cells of specialized connective tissues

Skeletal tissues, cartilage and bone are generally classified with the connective tissues, but their structure and functions are highly specialized and they are described inChapter 5. As with the general connective tissues, these specialized types are characterized by their extracellular matrix, which forms the major component of the tissues and is responsible for their properties. The resident cells are different from those in general connective tissues. Cartilage is populated by chondroblasts, which synthesize the matrix, and by mature chondrocytes. Bone matrix is elaborated by osteoblasts. Their mature progeny, osteocytes, are embedded within the matrix, which they help to mineralize, turn over and maintain. A third cell type, the osteoclast, has a different lineage origin and is derived from haemopoietic tissue; osteoclasts are responsible for bone degradation and remodelling in collaboration with osteoblasts.

Stiffness

Mark V. Lombardi , Lynn Phillippi , in Geriatric Rehabilitation Manual (Second Edition), 2007

Myofibroblasts

Connective tissue cells that produce unusually large amounts of contractile proteins are termed myofibroblasts. When damage occurs in connective tissue, there are two stages of response: cell multiplication and increased cellular secretion. If hyperplasia creates excessive production of actomyosin, the resulting contractile force may be significant enough to prevent normal range of motion in the affected area.

In addition, numerous studies describe the natural loss of muscle mass in the aged. While loss of muscle mass has been identified as a natural occurrence in the aged, recent studies support strength training in the aged as a means of reversing or preventing declines associated with aging. It is important to note that studies estimate that the rate of muscle mass loss exceeds 3–5% per decade after age 60 years. Also, strength loss is estimated to reach 30% per decade after age 60 years (Watson 2000, Brennan 2002). Strength loss studies suggest that traditional aerobic and endurance training activities employed in rehabilitation, while effective in the reduction of coronary heart disease, may also contribute to positive changes in both muscle strength and bone density (Wallace & Cumming 2000, Kean et al 2004).

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Benign Fibroblastic/Myofibroblastic Proliferations, Including Superficial Fibromatoses

John R. Goldblum MD , in Enzinger and Weiss's Soft Tissue Tumors , 2020

Keywords

acral fibromyxoma

angiofibroma

cranial fasciitis

Dupuytren disease

elastofibroma

Gardner-associated fibroma

intravascular fasciitis

ischemic fasciitis

keloid

knuckle pads

mammary-type myofibroblastoma

nodular fasciitis

nuchal-type fibroma

ossifying fasciitis

palisaded myofibroblastoma

palmar fibromatosis

penile fibromatosis

Peyronie disease

plantar fibromatosis

pleomorphic fibroma

proliferative fasciitis

proliferative myositis

pseudosarcomatous myofibroblastic proliferation

Functional Cell Biology

P.A. Janmey , ... R.T. Miller , in Encyclopedia of Cell Biology, 2016

Introduction

Connective tissue cells and matrices are distributed throughout the bodies of mammals and other metazoans and play key roles in organizing and supporting tissues and organs. Connective tissue matrices provide continuity with other cells and transduce chemical and physical stimuli that regulate cell activity. While extracellular matrices may appear to be inert, many matrices are highly dynamic and undergo remodeling as a result of cell-mediated synthesis and remodeling. The remodeling of the connective tissue matrix is essential for preserving healthy tissues and organs throughout life. Disturbances of matrix remodeling are involved in a vast array of inflammatory, neoplastic, and atrophic diseases ( McCarty et al., 2012; Hopps and Caimi, 2012; Eckhouse and Spinale, 2011; Lu et al., 2011) which arise in part from the diverse structure and function of matrix molecules and the complex behavior of connective tissue cells that are responsible for the remodeling of the matrix.

When seen from the top, a cell that is deposited from a three-dimensional suspension onto a flat surface can bind and spread along the surface in a manner that can closely resemble that of a liquid drop wetting a surface (Sackmann and Bruinsma, 2002) or a phospholipid vesicle flattening on a surface to which it adheres (Sackmann and Smith, 2014; Bell and Torney, 1985). In all three cases objects that are approximately spherical in three-dimensional suspension become flattened as they adhere to the surface, but eventually reach a finite area that is determined by a balance of forces that reach equilibrium or at least a steady state when the adhesive energy at the interface becomes comparable to the mechanical work required to deform a viscoelastic cell or a lipid droplet with surface tension (Sackmann and Smith, 2014). In some cases of single cells or even spherical aggregates of cells adhering to appropriate surfaces, the rates and extents to which the cells adhere and spread are similar to those of viscoelastic liquid drops wetting a surface (Douezan et al., 2011), but there are also many structural and thermodynamic differences between a cell or a cell aggregate and a simple liquid drop (Beaune et al., 2014). One important difference is that even when cells adhere to molecularly flat surfaces the adhesive interface is not flat and continuous but rather is formed by small discrete regions of the basal cell membrane that may be in close contact with the substrate, leaving the rest of the cell membrane unbound to the substrate and often fluctuating distances of several hundred nanometers above the surface, as has been well documented by reflection interference microscopy (Curtis, 1964), and other methods. A second important difference between microscopic cells and macroscopic liquid drops is that the cell membrane is small and soft enough to undergo significant thermal fluctuations as well as molecular motor-driven nonthermal motions whereas a macroscopic liquid drop surface is usually too large to be governed by factors other than its surface tension. A further essential difference is that the chemistry of drops wetting the surface is often driven by a uniform set of interactions between molecular structures that are very closely spaced, and can often be reasonably modeled as continuous interfaces, whereas cell–substrate or cell–matrix interactions are dictated largely by highly specific interactions between a well-defined set of transmembrane proteins and their unique set of ligands, as discussed in examples cited below, and these specific receptor-ligand bonds are often spaced many nanometers apart even in those regions of the cell membrane that make close contact with the surface (Geiger et al., 2009). A summary of the opposing interactions that control the cell–substrate interface is shown in Figure 1.

Figure 1. Summary of biochemical and mechanical effects mediating cell adhesion to surfaces.

 Reproduced with permission from Sackmann, E., Bruinsma, R.F., 2002. Cell adhesion as wetting transition? ChemPhysChem 3, 262–269.

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Mast Cells

Gary S. Firestein MD , in Firestein & Kelley's Textbook of Rheumatology , 2021

Mast Cells and Connective Tissue

Wound Healing and Tissue Fibrosis

Mast cells have long been noted to accumulate at the borders of healing wounds. In healthy human subjects undergoing experimental wounding and recurrent biopsies, mast cell numbers increase sixfold by day 10 after the initial incision. These mast cells localize preferentially to fibrotic areas of the wound and strongly express IL-4, a cytokine capable of inducing fibroblast proliferation and collagen synthesis. 95 In vitro studies confirm the stimulatory effects of mast cells on fibroblast growth; candidate fibroblast mitogens in addition to IL-4 include tryptase, histamine, LTC4, and bFGF. Indeed, W/Wv animals exhibit delayed contracture and healing of skin wounds in a manner reparable by local engraftment with cultured mast cells, though other mast cell–deficient mice exhibit no defect in wound healing. 96,97

Mast cells accumulate in sites of pathologic fibrosis, including the skin and lungs of patients with scleroderma. Because experimental skin fibrosis proceeds in mast cell–deficient mice with few if any differences in intensity or kinetics, it is unlikely that mast cells are an obligate effector lineage in human scleroderma, although they may contribute to disease progression. 98

Bone

Mast cells are also implicated in the remodeling of bone. Mast cells accumulate in sites of healing fracture and may contribute to normal bone turnover. 99,100 Mast cells accumulate in osteoporotic bone, and systemic osteoporosis is a known complication of systemic mastocytosis. 101,102 Heparin can directly promote differentiation and activation of osteoclasts. Mast cell products such as IL-1, TNF, and MIP-1α have similar activity.

Angiogenesis

Another potentially important activity of mast cells on the stroma is angiogenesis. Mast cells are not required for the development of the normal vasculature, as is evident in the viability of mast cell–deficient mice. However, mast cells cluster at sites of early blood vessel growth in tumors and contribute appreciably to physiologic angiogenesis under certain experimental conditions. Heparin was the first proangiogenic mast cell mediator identified; bFGF and VEGF are other potent stimulators of endothelial migration and proliferation.

Cardiac Cell Transplantation

Bryce H. Davis , ... Doris A. Taylor , in Cellular Transplantation, 2007

FIBROBLASTS

Fibroblasts are connective tissue cells that excrete extracellular matrix proteins and form underlying tissue stroma. In fact, fibroblasts, not cardiomyocytes, are the most abundant cell type in the human heart. Their use as preclinical therapeutic agents has primarily been to determine whether stable noncontractile cells can improve cardiac function. In our hands, transplanted dermal fibroblasts were able to improve material and diastolic properties of infarcted heart but were not able to improve systolic function [ 35]. This failure to improve contractility is likely due to fibroblasts' inability to contract, but cell-related improvements in diastolic dysfunction suggest that these cells may have a role in diastolic heart failure. Nonetheless, because fibroblast therapy was unable to improve systolic function these cells have not moved into clinical studies. Instead, noncontractile cells moved forward are those that have shown potential to differentiate into contractile cells.

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Scientific Fundamentals of Biotechnology

M.R. Mirbolooki , ... J.R.T. Lakey , in Comprehensive Biotechnology (Second Edition), 2011

1.44.6.2.1 Stromal cells

Stromal cells are connective tissue cells that form the supportive structure in which the functional cells of the tissue reside. Stromal cells can be isolated from a variety of tissues, such as bone marrow, periosteum, trabecular bone, synovium, skeletal muscle, deciduous teeth, and adipose tissues. Collagenase type I (from Clostridium histolyticum) is a crude collagenase preparation that can be used for the isolation of stromal cells. The preparation contains average amounts of caseinase, clostripain, and tryptic activities. To separate the human adipose-derived stromal cell (ASC) fraction from adipocytes, Traktuev et al. digested the tissues in collagenase type I solution under agitation for 2   h at 37   °C and centrifuged at 300 g for 8   min. They resuspended the pellet in DMEM–Ham's Nutrient Mixture F12 (DMEM–F12) containing 10% FBS, filtered it through 250-μm filters and centrifuged at 300 g for 8   min [1]. There are different versions of stromal cells isolation protocols available in the literature with minor differences. For instance, adipose tissues are treated with collagenase type I (1   mg   ml−1 in HBSS with 1% bovine serum albumin (BSA)) for just 60   min at 37   °C with intermittent shaking [34] or for 30–60   min at the same temperature with gentle agitation [7]. The pellet is centrifuged at the same g-force (300 g) but for a shorter time (5   min) [34] or at a higher g-force (400 g) and for a longer time (10   min) [20]. The activity of the collagenase is neutralized with DMEM-LG containing 10% fetal calf serum (FCS) [7]. The pellets are resuspended in a red blood cell lysis buffer (2.06   g   l−1 Tris base, 7.49   g   l−1 NH4Cl, pH 7.2) for 10   min at room temperature. The suspended cells are passed first through 100-µm and then through 40-µm cell sieves [20]. The prostatic stromal cells are also digested with collagenase type I (2   mg   ml−1) for 2.5   h at 37   °C on a shaking rotor. The tissue digest is vigorously pipetted and epithelial clumps settled from stromal cells for 15   min without centrifugation [24].

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Organ-Specific Toxicologic Pathology

John F. Van Vleet , ... Eugene Herman , in Handbook of Toxicologic Pathology (Second Edition), 2002

d. Cellular Components of Myocardial Interstitium

Fibroblasts are spindle-shaped connective tissue cells with a few cytoplasmic processes that extend in various directions and for varying distances into the surrounding connective tissue. Fibroblasts do not have an external lamina or basement membrane, and their surfaces frequently are in direct contact with collagen fibrils. Their major function is the synthesis of connective tissue proteins, particularly collagen.

Myofibroblasts resemble fibroblasts in most of their ultrastructural features but can be distinguished from the latter by their nuclear indentations and by the abundance of actin filaments in their cytoplasm. Myofibroblasts are thought to represent a type of cellular differentiation intermediate between fibroblasts and smooth muscle cells. In the heart, myofibroblasts are present in valvular and endocardial connective tissue.

Myocardial interstitium normally contains a small number of undifferentiated connective tissue cells, or primitive mesenchymal cells, which probably function as reserve cells, capable of responding to various stimuli by differentiating into other types of connective tissue cells.

Anitschkow cells are small and spindle shaped and have scant amounts of cytoplasm and poorly defined cell borders. Their distinguishing feature is related to their nuclei, which are oblong and contain a centrally located bar of chromatin. Nuclei showing this morphology are known as Anitschkow-type nuclei, caterpillar nuclei, or owl-eye nuclei. This nuclear morphology can also be found in cardiac muscle cells, endothelial cells, smooth muscle cells, Schwann cells and Aschoff cells. Our current concept is that Anitschkow cells are activated myocardial fibroblasts or fibroblast-like mesenchymal cells.

Macrophages (histiocytes) are normally present in small numbers in the myocardial interstitium and in the connective tissue of endocardium and valves. Mast cells are found in small numbers in myocardial interstitium, usually in perivascular locations, and in the endocardium.

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Systems Toxicologic Pathology

Brian R. Berridge , ... Eugene Herman , in Haschek and Rousseaux's Handbook of Toxicologic Pathology (Third Edition), 2013

Cellular Components of Myocardial Interstitium

Fibroblasts are spindle-shaped connective tissue cells with a few cytoplasmic processes that extend in various directions and for varying distances into the surrounding connective tissue. Fibroblasts do not have an external lamina or basement membrane, and their surfaces frequently are in direct contact with collagen fibrils. Their major function is the synthesis of connective tissue proteins, particularly collagen.

Myofibroblasts resemble fibroblasts in most of their ultrastructural features, but can be distinguished from the latter by their nuclear indentations and by the abundance of actin filaments in their cytoplasm. Myofibroblasts are thought to represent a type of cellular differentiation intermediate between fibroblasts and smooth muscle cells. In the heart, myofibroblasts are present in valvular and endocardial connective tissue.

Macrophages (histiocytes) are normally present in small numbers in the myocardial interstitium and in the connective tissue of endocardium and valves. Mast cells are found in small numbers in myocardial interstitium, usually in perivascular locations, and in the endocardium.

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Connective Tissues

Donald B. McMillan , Richard J. Harris , in An Atlas of Comparative Vertebrate Histology, 2018

Amorphous Intercellular Substances

1.

Ground substance . Connective tissue cells and fibers are embedded in an amorphous ground substance that is optically homogeneous and transparent when fresh; it is produced by fibroblasts and consists of proteoglycans and glycosaminoglycans of various types. It is extracted by ordinary fixatives and is not seen in most preparations. Proteoglycans contain sulfate groups and impart a metachromatic 1 property to ground substance when present in high concentrations. The ground substance of cartilage is composed principally of long proteoglycan–glycosaminoglycan chains associated with collagen fibrils; this provides rigidity to the tissue. The ground substance of bone is impregnated with crystals of hydroxyapatite [Ca10(PO4)6(OH)2].

2.

Tissue fluid. Connective tissue contains a transudate that seeps from blood plasma and constitutes one-third of the total body fluid (Fig. D46). Materials diffuse back and forth between the blood and cells of the connective tissues in this tissue fluid.

Figure D46. tissue fluid seeps back and forth between the blood plasma within blood capillaries and the surrounding tissues where it constitutes about one-third of the total body fluid. Excess fluids are drained by lymphatics that invade the tissues. hydrostatic pressure of the blood drives fluids out of capillaries; osmotic pressure, produced by the presence of colloids in the plasma within capillaries, but not in the tissue fluids, has an opposite effect on the fluids and draws them back into the capillaries. Under normal circumstances, a balance is affected between these two influences. If this balance is disturbed, e.g., by an obstruction of venous or lymphatic drainage, or by an increase in the accumulation of colloids in the tissues, the tissue may swell and become edematous. crystalloids, (largely sodium chloride) and dissolved gases are present in similar amounts in the plasma and tissue fluid and have little effect on fluid exchange.

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