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. 2020 Oct 6;21(19):7374.
doi: 10.3390/ijms21197374.

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

Gilberto Y Nakama  1 , Sabrina Gonzalez  1 , Polina Matre  2 , Xiaodong Mu  2 , Kaitlyn E Whitney  1   3 , Hajime Utsunomiya  1 , Justin W Arner  3 , Marc J Philippon  3 , Sudheer Ravuri  1 , Johnny Huard  1
Affiliations

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

Gilberto Y Nakama et al. Int J Mol Sci. .

Abstract

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).

Keywords: bone marrow concentrate (BMC); fibrosis; leukocyte-poor platelet-rich plasma (LP-PRP); losartan; transforming growth factor-1 beta (TGF-β1).

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Conflict of interest statement

The authors declare no conflict of interest. M.J.P. receives royalties from Smith & Nephew, Linvatec, Bledsoe, Arthrex, Encore Medical, DonJoy, and Arthrosurface; is a paid consultant for Smith & Nephew and MIS; owns stock or stock options in Smith & Nephew, Arthrosurface, HIPCO, and MIS; has received travel support from Siemens; has received research or institutional support from Smith & Nephew, Siemens, Ossur, and Arthrex. J.H. receives royalties from Cook Myosite Inc. G.Y.N., S.G., P.M., X.M., K.E.W., H.U., J.W.A., and S.R. declare no conflicts of interest.

Figures

Figure 1
Figure 1
Losartan and control group comparison of transforming growth factor-beta 1 (TGF-β1) levels in whole blood (WB) and leukocyte-poor platelet-rich plasma (LP-PRP).
Figure 2
Figure 2
CD31+ cells and CD45+ cells in bone marrow concentrate (BMC) comparing the losartan group to the control group. * p < 0.05.
Figure 3
Figure 3
Mesenchymal stem cells (MSCs), CD146+ cells and CD45+ CD34+ cells in bone marrow concentrate (BMC) comparing the losartan group to the control group. Results were not statistically different between groups.
Figure 4
Figure 4
Demonstration of the peripheral blood separation and resulting layers after the first and second centrifugation steps. Leukocyte-poor platelet-rich plasma (LP-PRP); platelet-poor plasma (PPP); red blood cells (RBCs).
Figure 5
Figure 5
Demonstration of the bone marrow separation and resulting layers after the first and second centrifugation steps. Bone marrow concentrate (BMC); platelet-poor plasma (PPP); red blood cells (RBCs).
See this image and copyright information in PMC

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