Basis of hematopoietic defects in platelet-derived growth factor (PDGF)-B and PDGF β-receptor null mice

Kaminski, Wolfgang E.; Lindahl, Per; Lin, Nancy; Broudy, Virginia C.; Crosby, Jeff; Hellström, Mats; Swolin, Birgitta; Bowen‐Pope, Daniel F.; Martin, Paul J.; Ross, Russell; Betsholtz, Christer; Raines, Elaine W.

doi:10.1182/blood.v97.7.1990

Cited by 67 publications

(56 citation statements)

References 57 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By creating a chimeric mouse knockout model using previously described methods [16,17], we successfully disrupted the production of PDGF-B in myeloid lineage cells prior to implantation of a cell-free scaffold. Grafts taken from PGDF-KO mice demonstrate a larger total TEVG area, likely explained by a higher amount of remaining scaffold as well as a decreased neointimal area, and decreased ECM deposition after 2 weeks compared with WT controls.…”

Section: Discussionmentioning

confidence: 99%

The Role of Myeloid Cell-Derived PDGF-B in Neotissue Formation in a Tissue-Engineered Vascular Graft

et al. 2017

View full text Add to dashboard Cite

Aim: Inflammatory myeloid lineage cells mediate neotissue formation in tissueengineered vascular grafts, but the molecular mechanism is not completely understood. We examined the role of vasculogenic PDGF-B in tissue-engineered vascular graft neotissue development. Materials & methods: Myeloid cell-specific PDGF-B knockout mice (PDGF-KO) were generated using bone marrow transplantation, and scaffolds were implanted as inferior vena cava interposition grafts in either PDGF-KO or wildtype mice. Results: After 2 weeks, grafts from PDGF-KO mice had more remaining scaffold polymer and less intimal neotissue development. Increased macrophage apoptosis, decreased smooth muscle cell proliferation and decreased collagen content was also observed. Conclusion: Myeloid cell-derived PDGF contributes to vascular neotissue formation by regulating macrophage apoptosis, smooth muscle cell proliferation and extracellular matrix deposition. Progress in tissue engineering continues to promise a solution to the lack of tissue available for reconstructive and replacement surgery. Our lab has worked over the past several years developing a tissue-engineered vascular graft (TEVG) for use in congenital heart and vascular surgery. Traditionally used prosthetic materials in the form of Dacron ® or Gore-Tex ® pose significant risk for thromboembolic and infectious complications and also lack growth capacity, making them less ideal for use in the pediatric population. Our ability to create a TEVG with growth capacity [1,2] has therefore been an important advancement in the field, but graft stenosis continues to be a major limitation to widespread clinical application. We have therefore concentrated our efforts on understanding the underlying processes of TEVG neotissue formation and stenosis development.We developed a murine model of TEVG stenosis [3] and found that seeding the grafts with bone marrow-derived mononuclear cells prior to implantation increases graft patency [4] in a dose responsive manner [5], but the seeded cells disappear shortly after implantation [6,7]. We thus hypothesized that a paracrine mechanism, rather than proliferation of seeded cells, was responsible for the remodeling of the TEVG and then demonstrated that host endothelial and smooth muscle cells from the adjacent vessel migrate to form the TEVG neotissue.Host monocytes and macrophages were identified as key mediators of graft remodeling. They infiltrate the graft in large numbers shortly after implantation, and excessive infiltration leads to graft stenosis [8].

show abstract

Section: Discussionmentioning

confidence: 99%

The Role of Myeloid Cell-Derived PDGF-B in Neotissue Formation in a Tissue-Engineered Vascular Graft

et al. 2017

View full text Add to dashboard Cite

show abstract

“…29,30 We have already found that lack of PDGF B-chain expression by hematopoietic cells and their progenitors does not affect the establishment of a normal hematopoietic system in the host mice, with platelets and all leukocyte cell types present at their normal levels. 29 The hematopoietic BϪ/Ϫ chimeras are expected to show no PDGF B-chain expression in platelets, macrophages, or other hematopoietic derivatives, but expression of PDGF B-chain in nonhematopoietic cell types, including ECs, should be normal. To verify the absence of PDGF B-chain from hematopoietic cells, we isolated peritoneal macrophages and evaluated B-chain transcript levels by semiquantitative reverse transcriptase-polymerase chain reaction.…”

Section: Pdgf B-chain Levels Are Significantly Reduced In Granulationmentioning

confidence: 99%

“…Recipients were transferred to conventional housing 6 to 8 weeks after transplantation. Complete replacement of host with donor hematopoietic cells had occurred by 3 months 29 and all experiments were performed after this time.…”

Section: Creation Of Hematopoietic Chimerasmentioning

confidence: 99%

“…Hematopoietic chimeras lacking PDGF B-chain expression in cells of hematopoietic origin (hematopoietic BϪ/Ϫ chimeras) were created as previously described. 29 Briefly, 129SV-C57BL/6J PDGF B-chain ϩ/Ϫ heterozygotes were mated and E16.5 embryos collected and genotyped. Livers from PDGF B-chain ϩ/ϩ and Ϫ/Ϫ embryonic littermates were disaggregated as a source of hematopoietic progenitors.…”

Section: Creation Of Hematopoietic Chimerasmentioning

confidence: 99%

“…Because these cells are of hematopoietic origin, we could specifically eliminate their ability to provide PDGF by creating hematopoietic chimeras, in which the hematopoietic system of a wild-type mouse was ablated by irradiation and replaced by hematopoietic cells from PDGF B-chain Ϫ/Ϫ mice. 29 We were surprised to find that the lack of PDGF B-chain of hematopoietic origin did not reduce the granulation tissue that formed in two models of response to injury: implantation of a sponge and formation of an organized intravascular thrombus. In fact, the absence of PDGF B-chain from hematopoietic cells actually increased the extent of vascularization of these lesions.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Platelet-Derived Growth Factor B-Chain of Hematopoietic Origin Is Not Necessary for Granulation Tissue Formation and Its Absence Enhances Vascularization

Buetow

Crosby

Kaminski

et al. 2001

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

The hypothesis that wound repair is augmented by delivery of platelet-derived growth factor (PDGF) from platelets and macrophages is an attractive extrapolation from the known activities of PDGF in cell culture and in vivo. To test this hypothesis in mice, we prepared hematopoietic chimeras, in which the hematopoietic system of a normal adult mouse was replaced by the hematopoietic system of a PDGF Bchain ؊/؊ or ؉/؉ donor. We initiated local granulation tissue formation either by implanting small surgical sponges to elicit a foreign body granulation tissue response, or by ligating the left common carotid to form an organized thrombus. We found that the absence of hematopoietic PDGF B-chain did not decrease the extent of granulation tissue or vascular lesion formation, and that the vascularization of both lesions increased by ϳ100%. We conclude that PDGF B-chain from cells of hematopoietic origin, including platelets and macrophages, is not important for granulation tissue formation, and that it reduces vascularization of granulation issue, probably through disabling of the short-range chemotactic gradients of PDGF that are important for recruiting peri-

show abstract

Cardiac pericytes function as key vasoactive cells to regulate homeostasis and disease

Lee

Khakoo²,

Chintalgattu

2020

FEBS Open Bio

View full text Add to dashboard Cite

EC-endothelial cell; PC-pericyte; SMC-smooth muscle cell; NG2-neural glial 2; PDGFRβ-platelet derived growth factor receptor beta; FACS-fluorescence activated cell sorting; HIF-1α-hypoxia inducible factor 1 alpha; VEGF-A-vascular endothelial growth factor-A; PDGFbb-platelet derived growth factor bb; α-SMAalpha smooth muscle actin; MI-myocardial infarction; LDL-low density lipoprotein; DMEM-Dulbecco's modified eagle media; P/S-penicillin/streptomycin; EGM-2-endothelial growth medium 2; FBS-fetal bovine serum; TEER-transepithelial electrical resistance; PE-phenylephrine; ADFP-adipose differentiationrelated protein; CCL2-CC motif chemokine ligand 2; TNFα-tumour necrosis factor alpha Running heading Cardiac pericytes are vasoregulators.

show abstract

Basis of hematopoietic defects in platelet-derived growth factor (PDGF)-B and PDGF β-receptor null mice

Cited by 67 publications

References 57 publications

The Role of Myeloid Cell-Derived PDGF-B in Neotissue Formation in a Tissue-Engineered Vascular Graft

The Role of Myeloid Cell-Derived PDGF-B in Neotissue Formation in a Tissue-Engineered Vascular Graft

Platelet-Derived Growth Factor B-Chain of Hematopoietic Origin Is Not Necessary for Granulation Tissue Formation and Its Absence Enhances Vascularization

Cardiac pericytes function as key vasoactive cells to regulate homeostasis and disease

Contact Info

Product

Resources

About