TY - JOUR
T1 - Effect of oral losartan on orthobiologics
T2 - Implications for platelet-rich plasma and bone marrow concentrate—a rabbit study
AU - Nakama, Gilberto Y.
AU - Gonzalez, Sabrina
AU - Matre, Polina
AU - Mu, Xiaodong
AU - Whitney, Kaitlyn E.
AU - Utsunomiya, Hajime
AU - Arner, Justin W.
AU - Philippon, Marc J.
AU - Ravuri, Sudheer
AU - Huard, Johnny
N1 - Funding Information:
Funding: This study was funded by the Steven Read Foundation.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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).
AB - 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).
KW - Bone marrow concentrate (BMC)
KW - Fibrosis
KW - Leukocyte-poor platelet-rich plasma (LP-PRP)
KW - Losartan
KW - Transforming growth factor-1 beta (TGF-β1)
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U2 - 10.3390/ijms21197374
DO - 10.3390/ijms21197374
M3 - Article
C2 - 33036225
AN - SCOPUS:85092237580
SN - 1661-6596
VL - 21
SP - 1
EP - 13
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 19
M1 - 7374
ER -