Fibroblasts and Mesenchymal Stromal/Stem Cells Are Phenotypically Indistinguishable

Denu, Ryan A.; Nemcek, Steven P.; Dd, Bloom; Ad, Goodrich; Kim, Jaehyup; Df, Mosher; Hematti, Peiman

doi:10.1159/000445096

Cited by 175 publications

(147 citation statements)

References 61 publications

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“…This could be explained by the presence of SC in the SCTLAS. Although these cells still need further characterization, previous works demonstrated that stromal cells fulfill some of the ISCT minimal criteria for adult stem cells, including the capability for multipotent differentiation to osteogenic, chondrogenic, and adipogenic lineages . These cells could release a large number of growth factors including cytokines, chemokines involved in migration, expansion, and factors involved in immunomodulation and angiogenesis, as it has been described for mesenchymal SC .…”

Section: Discussionmentioning

confidence: 90%

Generation and Evaluation of Novel Stromal Cell‐Containing Tissue Engineered Artificial Stromas for the Surgical Repair of Abdominal Defects

Martín-Piedra

Garzón

Gómez-Sotelo

et al. 2017

Biotechnology Journal

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Repair of abdominal wall defects is one of the major clinical challenges in abdominal surgery. Most biomaterials are associated to infection and severe complications, making necessary safer and more biocompatible approaches. In the present work, the adequate mechanical properties of synthetic polymer meshes with tissue-engineered matrices containing stromal mesenchymal cells is combined to generate a novel cell-containing tissue-like artificial stroma (SCTLAS) for use in abdominal wall repair. SCTLAS consisting on fibrin-agarose hydrogels seeded with stromal cells and reinforced with commercial surgical meshes (SM) are evaluated in vitro and in vivo in animal models of abdominal wall defect. Inflammatory cells, collagen, and extracellular matrix (ECM) components are analyzed and compared with grafted SM. Use of SCTLAS results in less inflammation and less fibrosis than SM, with most ECM components being very similar to control abdominal wall tissues. Cell migration and ECM remodeling within SCTLAS is comparable to control tissues. The use of SCTLAS could contribute to reduce the side-effects associated to currently available SM and regenerated tissues are more similar to control abdominal wall tissues. Bioengineered SCTLAS could contribute to a safer treatment of abdominal wall defects with higher biocompatibility than currently available SM.

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Section: Discussionmentioning

confidence: 90%

Generation and Evaluation of Novel Stromal Cell‐Containing Tissue Engineered Artificial Stromas for the Surgical Repair of Abdominal Defects

Martín-Piedra

Garzón

Gómez-Sotelo

et al. 2017

Biotechnology Journal

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“…Thus, the low‐level expression of negative markers seen in our testing could be due to a subset of cells positive for CD34, CD11b, CD19, or HLA‐DR. A separate study showed comparable results, indicating similar expression of MSC‐defining cell surface antigens between FBs and MSCs. Overall, human MSCs and FBs are similar in regards to their expression of MSC surface markers.…”

Section: Discussionmentioning

confidence: 75%

“…Another criterion used to define MSCs is the ability to differentiate into multiple cell types under appropriate conditions, including bone, adipose, and cartilage . Previous reports generated conflicting results when FB cell populations were differentiated in culture . Although some reports conclude that FBs are not capable of in vitro differentiation, several studies indicate that they behave similarly to MSCs when differentiated under the same conditions .…”

Section: Discussionmentioning

confidence: 99%

Human primary fibroblasts perform similarly to MSCs in assays used to evaluate MSC safety and potency

et al. 2019

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BACKGROUND Cellular therapeutic agents may benefit trauma patients by modulating the immune response to injury, and by reducing inflammation and vascular leakage. Administration of allogeneic mesenchymal stromal cells (MSCs) shows some benefit in preclinical and clinical trials, but less testing has been performed with other cell types. Human primary fibroblasts (FBs) were compared to MSCs in assays designed to evaluate MSCs to determine if these assays actually evaluate properties unique to MSCs or whether related cell types perform similarly. STUDY DESIGN AND METHODS MSC‐related surface marker expression, tissue factor, and human leukocyte antigen–D related were evaluated by flow cytometry, and in vitro adipogenic and osteogenic differentiation potential were determined. Procoagulant activity was determined by thromboelastography. Two potency assays correlated with immunomodulation potential were utilized: the mixed lymphocyte reaction and indoleamine 2,3‐dioxygenase enzyme activity assays. RESULTS Human primary FBs performed similarly to MSCs in assays designed to evaluate MSC characteristics and potency. Although similar for MSC‐positive cell surface marker expression, FBs did not show robust adipose differentiation and expressed some level of markers not expected on MSCs. CONCLUSIONS Human primary FBs are very similar to human MSCs, at least in assays currently used to evaluate MSC potency. Preclinical and clinical testing are required to determine if FBs show similar activity to MSCs in vivo. If FBs show inferior activity in vivo, development of new MSC‐specific potency assays will be necessary to evaluate properties relevant to their unique clinical benefits.

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“…In vitro , mesenchymal stem cells and fibroblasts had a similar morphology and expressed several of the same cell surface markers, both deposit collagen type I, and both were capable of differentiating into chondrocytes and osteoblasts (Denu et al. ). Although this cannot be assumed to be the case in vivo , these studies tentatively support the suggestion that mesenchymal cells within cartilage canals may have fibroblast‐like properties and be capable of producing collagen type I, en route to becoming chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

Cartilage canals in the distal intermediate ridge of the tibia of fetuses and foals are surrounded by different types of collagen

et al. 2017

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Some epiphyseal growth cartilage canals are surrounded by a ring of hypereosinophilic matrix consisting of collagen type I. Absence of the collagen type I ring may predispose canal vessels to failure and osteochondrosis, which can lead to fragments in joints (osteochondrosis dissecans). It is not known whether the ring develops in response to programming or biomechanical force. The distribution that may reveal the function of the ring has only been described in the distal femur of a limited number of foals. It is also not known which cells are responsible for producing the collagen ring. The aims of the current study were to examine fetuses and foals to infer whether the ring forms in response to biomechanical force or programming, to describe distribution and to investigate which cell type produces the ring. The material consisted of 46 fetuses and foals from 293 days of gestation to 142 days old, of both sexes and different breeds, divided into three groups, designated the naïve group up to and including the day of birth, the adapting group from 2 days up to and including 14 days old, and the loaded group from 15 days and older. The distal tibia was sawn into parasagittal slabs and the cranial half of the central slab from the intermediate ridge was examined by light microscopy and immunohistochemical staining for collagen type I. Presence, completeness and location of the collagen ring was compared, as was the quantity of perivascular mesenchymal cells. An eosinophilic ring present on HE‐stained sections was seen in every single fetus and foal examined, which corresponded to collagen type I in immunostained sections. A higher proportion of cartilage canals were surrounded by an eosinophilic ring in the naïve and adapting groups at 73 and 76%, respectively, compared with the loaded group at 51%. When considering only patent canals, the proportion of canals with an eosinophilic ring was higher in the adapting and loaded than the naïve group of foals. The ring was present around 90 and 81% of patent canals in the deep and middle layers, respectively, compared with 58% in the superficial layer, and the ring was more often complete around deep compared with superficial canals. The ring was absent or partial around chondrifying canals. When an eosinophilic ring was present around patent canals, it was more common for the canal to contain one or more layers of perivascular mesenchymal cells rather than few to no layers. It was also more common for the collagen ring to be more complete around canals that contained many as opposed to few mesenchymal cells. In conclusion, the proportion of cartilage canals that had an eosinophilic ring was similar in all three groups of fetuses and foals, indicating that the presence of the collagen ring was mostly programmed, although some adaptation was evident. The ring was more often present around deep, compared with superficial canals, indicating a role in preparation for ossification. The collagen ring appeared to be produced by perivascular mesenchymal cells.

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Fibroblasts and Mesenchymal Stromal/Stem Cells Are Phenotypically Indistinguishable

Cited by 175 publications

References 61 publications

Generation and Evaluation of Novel Stromal Cell‐Containing Tissue Engineered Artificial Stromas for the Surgical Repair of Abdominal Defects

Generation and Evaluation of Novel Stromal Cell‐Containing Tissue Engineered Artificial Stromas for the Surgical Repair of Abdominal Defects

Human primary fibroblasts perform similarly to MSCs in assays used to evaluate MSC safety and potency

Cartilage canals in the distal intermediate ridge of the tibia of fetuses and foals are surrounded by different types of collagen

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