The Development of Pure Cultures of Fibroblasts From Single Mononuclear Cells

Moen, Johannes K.

doi:10.1084/jem.61.2.247

Cited by 32 publications

(10 citation statements)

References 6 publications

(8 reference statements)

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“…The source of the fibroblast in healing wounds The source of the connective tissue-forming cell in healing wounds has been a matter for debate since Cohnheim ( I 867) suggested that cells from the blood may serve as progenitors for fibroblasts. This same notion has since been proposed by many investigators (Fischer, 1925 ;Maximow, 1927;Carrel & Ebeling, 1926;Bloom, 1927; 1928; Moen, 1935;Allgower, 1956; Allgower & Hulliger, 1960; Petrakis, Davis & Lucia, 1961; Petrakis, 1961). Most attempts to study this problem have utilized modifications of various techniques of tissue culture, or examination of blood cells, usually obtained from the buffy coat, grown in subcutaneously implanted Millipore filter diffusion chambers.…”

Section: The Proliferative Phasementioning

confidence: 80%

The Fibroblast and Wound Repair

Ross¹

1968

Biological Reviews

402

128

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Summary This review of connective tissue repair has attempted to place into historical perspective information obtained by newer approaches. The literature review is incomplete, as it was unfortunately necessary to leave many interesting studies out of the discussion. Emphasis has been placed upon what is known of the inflammatory response, the fine structure of the connective tissue cells in healing wounds and with correlated chemical findings in these tissues. An optimal inflammatory response appears to be an important, rapid, non‐specific stimulus for fibroplasia. It is not clear how inflammation exerts this effect. The inflammatory cells and their enzymes markedly alter the extracellular matrix of injured tissue. The matrix of connective tissue may itself participate in the control of its own synthesis and degradation. It is possible that modification of this environment by injury and/or inflammation with ensuing matrix alteration may provide a stimulus for cell migration and protein synthesis. The converse may also be true, that is, a given level of matrix concentration may have an inhibitory effect upon the connective tissue cells. The inter‐relationships between the connective tissue matrix and the cells, and the possibilities of feedback mechanisms playing a role in maintaining a balance between these two are important areas for future investigation. In this regard, additional questions may be asked concerning the role of the fibroblast in remodelling and degradation of connective tissue. It is not yet clear how important a balance between collagenolytic enzymes and the solubility states, or stability, of collagen are in each connective tissue. It will be interesting to determine which cells make collagenolytic and/or proteolytic enzymes upon appropriate stimulus. It is possible to distinguish between the fibroblast and the monocyte, or potential macrophage with the electron microscope. The rough endoplasmic reticulum with its large numbers of attached ribosomes is extensively developed in the fibroblast in contrast to the monocyte. The endoplasmic reticulum sequesters collagen precursors and other secretory proteins for transport either directly to the extracellular space, as appears to be the case for collagen, or to the Golgi complex as is the case for other exportable proteins. Collagen precursors are secreted into the environment and are not shed from within the cell surface. A number of cytoplasmic alterations have been described for fibroblasts and other cells during various pathological states. The significance of these alterations is not clear. It will be important to distinguish between specific and non‐specific responses to injury, if these alterations are to aid us in understanding the various cellular responses. The source of the fibroblasts in granulation tissue appears to be mesenchymal cells from adjacent tissues rather than blood‐borne precursors. Although contact inhibition can be demonstrated in vitro, it is not clear how important this phenomenon is in vivo, nor are the reasons for the...

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Section: The Proliferative Phasementioning

confidence: 80%

The Fibroblast and Wound Repair

Ross¹

1968

Biological Reviews

402

128

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“…It was thought that wound fibroblasts were derived from circulating blood cells rather than local tissue stroma. Cultures of buffy coat preparations from blood or bone marrow suggested that circulating cells could differentiate into fibroblasts or other mesenchymal cells 85,86. This hypothesis was rejected by Ross and Lillywhite87 who concluded that the ability to grow fibroblast‐like cells from buffy coat preparations depended on how the blood was collected.…”

Section: Do Myofibroblasts Originate From Circulating Stem Cells?mentioning

confidence: 99%

“…Cultures of buffy coat preparations from blood or bone marrow suggested that circulating cells could differentiate into fibroblasts or other mesenchymal cells. 85,86 This hypothesis was rejected by Ross and Lillywhite 87 who concluded that the ability to grow fibroblast-like cells from buffy coat preparations depended on how the blood was collected. Blood collection by arterial catheterization resulted in few, if any, fibroblasts from the circulating cells compared to blood obtained by cardiac puncture.…”

Section: Do Myofibroblasts Originate From Circulating Stem Cells?mentioning

confidence: 99%

Perivascular Responses after Angioplasty Which May Contribute to Postangioplasty Restenosis

Wilcox

Okamoto

Nakahara

et al. 2001

Annals of the New York Academy of Sciences

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These studies suggest that the adventitia may play a role in vascular lesion formation after balloon overstretch injury of pig coronary arteries by contributing to the cellular mass of the neointima and the synthesis of growth factors. In addition, the adventitia may contribute to vascular remodeling and constriction of the external elastic lamina through accumulation of myofibroblasts containing alpha smooth muscle actin in the adventitia surrounding the injury site. Inhibition of myofibroblast proliferation and/or recruitment by intravascular brachytherapy positively affects vascular remodeling through its action on adventitial cells. Inflammation is a major event associated with balloon angioplasty, resulting in the sequential recruitment of neutrophils (2‐24 hours) and monocyte/macrophages (24‐72 hours) predominantly into the adventitia surrounding the injury site. It is hypothesized that inflammatory cells release cytokines and/or increase the production of superoxides which stimulate the proliferation and recruitment of adventitial myofibroblasts. Inflammatory and proliferative responses were not confined to the local adventitia but were found extending as far as 1‐3 mm away from the injured vessel in the distal perivascular tissues. Studies were performed to examine the expression of genes associated with cell migration at early times after injury in an attempt to determine the source of the adventitial myofibroblasts. Expression of genes involved in cell migration including MMP‐2, MMP‐9, and tenascin was found as early as 2 hours following angioplasty in the intramyocardial, pericardial, and adipose tissue fibroblasts. While these studies suggest that local tissue was the source of the myofibroblasts recruited to the injury site, we have been unable to confirm this finding by direct fluorescent labeling of adventitial cells. Recent work from our laboratory suggests that myofibroblast precursors may be isolated from buffy coat preparations from peripheral blood. These results lead us to hypothesize that stem cells that differentiate into myofibroblasts may be recruited in early inflammatory infiltrates in the adventitia. Clearly, additional work will have to be directed at a more detailed examination of the response of adventitial and other perivascular cells and tissues to balloon injury to determine their sources and their role in regulating vascular lesion development.

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“…It is not difficult to visualize how some environmental conditions, such as the source of dialyzed serum, may influence the outcome of this delicate balance. The concept of cellular interdependence is well known among the developmental biologists (28), tissue culture investigators (29), and bacteriologists (30).…”

Section: Discussionmentioning

confidence: 99%

Genetic Study of Human Cells in Vitro

Chang

1960

The Journal of Experimental Medicine

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The isolation of carbohydrate variants from cultures of HeLa and conjunctival cells was described. Factors inherent in the cell culture system, such as parent populations and dialyzed serums, have been shown to influence the outcome of variant isolations. Established stable variants incorporated significantly more pentoses or lactate into various cell fractions than the parent cultures. Besides their abilities to propagate continuously in the selecting environments, the variants multiplied slower, were more susceptible to sub-zero preservation and the cytotoxic effect of D-2-deoxyglucose, showed lower cloning efficiencies and were less susceptible to the deleterious effect of glucose oxidase. The ribose variants also differed from the parent cultures in morphological appearance such as formation of multinucleated cells and ring-shaped colonies. They converted more ribose into other component sugars of mucopolysaccharides than the parent cultures. Preliminary analyses of the mucopolysaccharides extracted from the ribose variants and parent cultures showed large difference in their carbohydrate (Molisch-positive materials) and DNA ratios. Evidence suggests that a sequence of interrelated events from genetic selection to primitive morphogenesis has been established.

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The Development of Pure Cultures of Fibroblasts From Single Mononuclear Cells

Cited by 32 publications

References 6 publications

The Fibroblast and Wound Repair

The Fibroblast and Wound Repair

Perivascular Responses after Angioplasty Which May Contribute to Postangioplasty Restenosis

Genetic Study of Human Cells in Vitro

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