Delivery of TGF-β1 and GH from Mineralized PCL Films; A Potential Novel Model of Gelatinous Transformation of the Bone Marrow

2019 ◽  
Author(s):  
Matthew B. Parlato ◽  
David G. Belair ◽  
Gianluca Fontana ◽  
Ellen Leiferman ◽  
Rewais Hanna ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Novel Model ◽  
Tgf Β1 ◽  
Gelatinous Transformation

scholarly journals Effect of Oral Losartan on Orthobiologics: Implications for Platelet-Rich Plasma and Bone Marrow Concentrate—A Rabbit Study

2020 ◽  
Vol 21 (19) ◽  
pp. 7374
Author(s):  
Gilberto Y. Nakama ◽  
Sabrina Gonzalez ◽  
Polina Matre ◽  
Xiaodong Mu ◽  
Kaitlyn E. Whitney ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Osteochondral Defect ◽  
Platelet Rich Plasma ◽  
Control Group ◽  
Bone Marrow Concentrate ◽  
Significant Difference ◽  
Losartan Group ◽  
Group 2 ◽  
And Control ◽  
Tgf Β1

Recent efforts have focused on customizing orthobiologics, such as platelet-rich plasma (PRP) and bone marrow concentrate (BMC), to improve tissue repair. We hypothesized that oral losartan (a TGF-β1 blocker with anti-fibrotic properties) could decrease TGF-β1 levels in leukocyte-poor PRP (LP-PRP) and fibrocytes in BMC. Ten rabbits were randomized into two groups (N = 5/group): osteochondral defect + microfracture (control, group 1) and osteochondral defect + microfracture + losartan (losartan, group 2). For group 2, a dose of 10mg/kg/day of losartan was administrated orally for 12 weeks post-operatively. After 12 weeks, whole blood (WB) and bone marrow aspirate (BMA) samples were collected to process LP-PRP and BMC. TGF-β1 concentrations were measured in WB and LP-PRP with multiplex immunoassay. BMC cell populations were analyzed by flow cytometry with CD31, CD44, CD45, CD34, CD146 and CD90 antibodies. There was no significant difference in TGF-β1 levels between the losartan and control group in WB or LP-PRP. In BMC, the percentage of CD31+ cells (endothelial cells) in the losartan group was significantly higher than the control group (p = 0.008), while the percentage of CD45+ cells (hematopoietic cells-fibrocytes) in the losartan group was significantly lower than the control group (p = 0.03).

scholarly journals Platelet TSP-1 Controls Prostate Cancer-Induced Osteoclast Differentiation and Bone Marrow-Derived Cell Mobilization through TGFβ-1

2020 ◽  
Author(s):  
Bethany A. Kerr ◽  
Koran S. Harris ◽  
Lihong Shi ◽  
Jeffrey S. Willey ◽  
David R. Soto-Pantoja ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Bone Formation ◽  
Tumor Growth ◽  
Tumor Size ◽  
Metastatic Niche ◽  
Primary Tumors ◽  
Niche Formation ◽  
Cell Mobilization ◽  
Tgf Β1

ABSTRACTThe development of distant metastasis is the main cause of prostate cancer (CaP)-related death with the skeleton being the primary site of metastasis. While the progression of primary tumors and the growth of bone metastatic tumors are well described, the mechanisms controlling pre-metastatic niche formation and homing of CaP to bone remain unclear. Through prior studies, we demonstrated that platelet secretion was required for ongoing tumor growth and pre-metastatic tumor-induce bone formation and bone marrow-derived cell mobilization to cancers supporting angiogenesis. We hypothesized that proteins released by the platelet α granules were responsible for inducing changes in the pre-metastatic bone niche. We found that the classically anti-angiogenic protein thrombospondin (TSP)-1 was significantly increased in the platelets of mice bearing tumors. To determine the role of increased TSP-1, we implanted tumors in TSP-1 null animals and assessed changes in tumor growth and pre-metastatic niche formation. TSP-1 loss resulted in increased tumor size and enhanced angiogenesis but reduced bone marrow-derived cell mobilization and tumor-induced bone formation with enhanced osteoclast formation. We hypothesized that these changes in the pre-metastatic niche were due to the retention of TGF-β1 in the platelets of mice with TSP-1 deleted. To assess the importance of platelet-derived TGF-β1, we implanted CaP tumors in mice with platelet-specific deletion of TGF-β1. Similar to TSP-1 deletion, loss of platelet TGF-β1 resulted in increased angiogenesis with a milder effect on tumor size and BMDC release. Within the bone microenvironment, platelet TGF-β1 deletion prevented tumor-induced bone formation due to increased osteoclastogenesis. Thus, we demonstrate that the TSP-1/TGF-β1 axis regulates pre-metastatic niche formation and tumor-induced bone turnover. Targeting the platelet release of TSP-1 or TGF-β1 represents a potential method to interfere with the process of CaP metastasis to bone.

scholarly journals Sa1711 – Bone Marrow-Derived Myofibroblasts Promotes Gastric Cancer Metastasis Through Activating TGF-Β1 and Il-6/Stat3 Signal Pathways

2019 ◽  
Vol 156 (6) ◽  
pp. S-374-S-375
Author(s):  
JIANZHENG WANG ◽  
Xiaojiao Cheng ◽  
BAIWEN ZHANG ◽  
JIACHENG LIN ◽  
YAO TANG ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bone Marrow ◽  
Cancer Metastasis ◽  
Signal Pathways ◽  
Tgf Β1

scholarly journals Pancytopenia with focal serous atrophy (gelatinous transformation) of the bone marrow

2014 ◽  
Vol 7 (2) ◽  
pp. 91-92
Author(s):  
Gregory P. Kaufman ◽  
Jeremy T. Larsen ◽  
Michelle A. Elliott ◽  
Matthew T. Howard
Keyword(s):  
Bone Marrow ◽  
Gelatinous Transformation

Gelatinous Transformation of Bone Marrow in Patients with Anorexia Nervosa

2013 ◽  
Vol 52 (17) ◽  
pp. 2005-2006 ◽  
Author(s):  
Kazuhiko Morii ◽  
Takeharu Yamamoto ◽  
Hiroshi Kishida ◽  
Hiroaki Okushin
Keyword(s):  
Bone Marrow ◽  
Anorexia Nervosa ◽  
Gelatinous Transformation

scholarly journals Autocrine/paracrine TGFβ1 is required for the development of epidermal Langerhans cells

2007 ◽  
Vol 204 (11) ◽  
pp. 2545-2552 ◽  
Author(s):  
Daniel H. Kaplan ◽  
Ming O. Li ◽  
Matthew C. Jenison ◽  
Warren D. Shlomchik ◽  
Richard A. Flavell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Langerhans Cells ◽  
Transforming Growth Factor ◽  
Artificial Chromosome ◽  
Accessory Cells ◽  
Epidermal Dendritic Cells ◽  
Deficient Mice ◽  
Tgf Β1 ◽  
Epidermal Langerhans Cells

Langerhans cells (LCs) are bone marrow (BM)–derived epidermal dendritic cells (DCs) that develop from precursors found in the dermis. Epidermal LCs are absent in transforming growth factor (TGF) β1-deficient mice. It is not clear whether TGFβ1 acts directly on LC precursors to promote maturation or whether it acts on accessory cells, which in turn affect LC precursors. In addition, the physiologic source of TGFβ1 is uncertain because BM chimera experiments showed that neither hematopoietic nor nonhematopoietic-derived TGFβ1 is required for LC development. To address these issues, we created mice transgenic for a bacterial artificial chromosome (BAC) containing the gene for human Langerin into which Cre recombinase had been inserted by homologous recombination (Langerin-Cre). These mice express Cre selectively in LCs, and they were bred to floxed TGFβRII and TGFβ1 mice, thereby generating mice with LCs that either cannot respond to or generate TGFβ1, respectively. Langerin-Cre TGFβRII mice had substantially reduced numbers of epidermal LCs, demonstrating that TGFβ1 acts directly on LCs in vivo. Interestingly, Langerin-Cre TGFβ1 mice also had very few LCs both in the steady state and after BM transplantation. Thus, TGFβ1 derived from LCs acts directly on LCs through an autocrine/paracrine loop, and it is required for LC development and/or survival.

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