Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative

The MSC: An Injury Drugstore

http://cellbanktech.com/wp-content/uploads/2014/02/10.-Meirelles-LD-et-al.-Mechanisms-involved-in-therapeutic-properties-of-mesenchymal-stem-cells.-in-Cytokine-Growth-Factor-Res-2009.pdf

Mechanisms involved in the therapeutic properties of mesenchymal stem cells

Adult marrow-derived mesenchymal stem cells (MSCs) are able to differentiate into bone, cartilage, muscle, marrow stroma, tendon-ligament, fat and other connective tissues. The questions can be asked, what do MSCs do naturally and where is the MSC niche? New insight and clinical experience suggest that MSCs are naturally found as perivascular cells, summarily referred to as pericytes, which are released at sites of injury, where they secrete large quantities of bioactive factors that are both immunomodulatory and trophic. The trophic activity inhibits ischaemia-caused apoptosis and scarring while stimulating angiogenesis and the mitosis of tissue intrinsic progenitor cells. The immunomodulation inhibits lymphocyte surveillance of the injured tissue, thus preventing autoimmunity, and allows allogeneic MSCs to be used in a variety of clinical situations. Thus, a new, enlightened era of experimentation and clinical trials has been initiated with xenogenic and allogeneic MSCs.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/path.2469

Why are MSCs therapeutic? New data: new insight

Wound healing is one of the most complex processes in the human body. It involves the spatial and temporal synchronization of a variety of cell types with distinct roles in the phases of hemostasis...

Wound Healing: A Cellular Perspective.

Dermal fibroblasts are a dynamic and diverse population of cells whose functions in skin in many respects remain unknown. Normal adult human skin contains at least three distinct subpopulations of fibroblasts, which occupy unique niches in the dermis. Fibroblasts from each of these niches exhibit distinctive differences when cultured separately. Specific differences in fibroblast physiology are evident in papillary dermal fibroblasts, which reside in the superficial dermis, and reticular fibroblasts, which reside in the deep dermis. Both of these subpopulations of fibroblasts differ from the fibroblasts that are associated with hair follicles. Fibroblasts engage in fibroblast-epidermal interactions during hair development and in interfollicular regions of skin. They also play an important role in cutaneous wound repair and an ever-increasing role in bioengineering of skin. Bioengineered skin currently performs important roles in providing (1) a basic understanding of skin biology, (2) a vehicle for testing topically applied products and (3) a resource for skin replacement.

/pdf/fibroblast-heterogeneity-more-than-skin-deep-5d60s2y4vf.pdf

Fibroblast heterogeneity: more than skin deep.

The capacity of fibroblasts to produce and organize the extracellular matrix and to communicate with other cells makes them a central component of tissue biology. Even so, fibroblasts remain a somewhat enigmatic population. Our inability to fully comprehend these cells is in large part due to the paucity of unique cellular markers and to their pervasive diversity. Much of our understanding of fibroblast diversity has evolved from studies where subpopulations of these cells have been produced without resorting to cell surface markers. In this regard, cloning and mechanical separation of tissues prior to establishing cultures has provided multiple subpopulations. Nonetheless, in isolated situations, the expression or lack of expression of Thy-1/CD90 has been used to separate fibroblast subsets. The role of fibroblasts in intercellular communication is emerging through the implementation of organotypic studies in which three-dimensional fibroblast culture are combined with other populations of cells. Such studies have revealed critical paracrine loops that are essential for organ development and for wound repair. These studies also provide a backdrop for the emerging field of tissue engineering. The participation of fibroblasts in the regulation of tissue homeostasis and their contribution to the aging process are emerging issues that require better understanding. In short, fibroblasts represent a multifaceted, complex group of cells.

Fibroblasts-a diverse population at the center of it all.

The effective delivery of bioactive molecules to wound sites hasten repair. Cellular therapies provide a means for the targeted delivery of a complex, multiple arrays of bioactive factors to wound sites. Thus, the identification of ideal therapeutic populations is an essential aspect of this approach. In vitro assays can provide an important first step toward this goal by selecting populations that are likely suitable for more expensive and time-consuming in vivo assays. In this study, bone marrow-derived mesenchymal stem cells (BM-MSCs) were integrated into a three-dimensional coculture system that supports the development and stabilization of vascular tube-like structures. The presence of a limited number of BM-MSCs resulted in their coalignment with vascular structures, and it further resulted in increased tubule numbers and complexity. Thus, these studies suggest that BM-MSCs functionally interacted with and were attracted to in vitro formed vascular structures. Further, these cells also provided sufficient bioactive factors and matrix molecules to support the formation of tubular arrays and the stabilization of these arrays. This in vitro system provides a means for assessing the function of BM-MSCs in aspects of the angiogenic component of wound repair.

/pdf/influence-of-adult-mesenchymal-stem-cells-on-in-vitro-p8fe8f5bec.pdf

Influence of Adult Mesenchymal Stem Cells on In Vitro Vascular Formation

Age-related Changes in the Proteoglycans of Human Skin

A multilayer skin equivalent is formed having a scaffold layer containing dermis-forming cells, and a keratinocyte layer. The dermis-forming cells and keratinocytes are preferably autologous, and the dermis-forming cells can be human mesenchymal stem cells (MSCs), dermal fibroblasts (e.g., papillary or reticular dermal fibroblasts) or mixtures thereof. The scaffold is preferably type I collagen alone, or types I and II collagen in combination. Also formed is a multilayer skin equivalent having a scaffold layer containing a layer of extracellular matrix component containing papillary dermal fibroblasts in laminar relationship with a layer of extracellular matrix component containing reticular dermal fibroblasts, and a keratinocyte layer. A multilayer dermal equivalent is provided having a layer of extracellular matrix component containing papillary dermis-forming cells and a layer of extracellular matrix component containing reticular dermis-forming cells. In another embodiment, the dermal equivalent has a layer containing MSCs and a layer selected from a layer of extracellular matrix component containing papillary dermis-forming cells and a layer of extracellular matrix component containing reticular dermis-forming cells, and optionally a keratinocyte layer. In the skin and dermal equivalents, at least one layer may contain an agent that promotes adhesion or angiogenesis. Also present may be a bioactive agent that enhances proliferation, commitment or differentiation of mesenchymal stem cells into dermal components, either in vitro or in vivo. An injectionable composition is also provided containing dermis-forming cells and an extracellular matrix component in a pharmaceutically acceptable injectable carrier.

J. Michael Sorrell

Papers

Fibroblast heterogeneity: more than skin deep.

Fibroblasts-a diverse population at the center of it all.

Influence of Adult Mesenchymal Stem Cells on In Vitro Vascular Formation

Age-related Changes in the Proteoglycans of Human Skin

Multilayer skin or dermal equivalent having a layer containing mesenchymal stem cells