Author(s): Salazar KD, Lankford SM, Brody AR
Studies have been carried out previously to determine whether mesenchymal stem cells (MSC) influence the progression of pulmonary fibrosis. Here, we asked whether MSC (derived from mouse bone marrow and human umbilical cord blood) produce factors that mediate lung fibroblast (LF) growth and matrix production. MSC-conditioned media (CM) were found by ELISA to contain significant amounts of PDGF-AA and transforming growth factor-beta1 (TGF-beta1). Proliferation was increased in a concentration-dependent manner in LF cell lines and primary cells cultured in MSC-CM, but neither anti-PDGF antibodies nor PDGF receptor-specific antibodies affected proliferation, nor did a number of other antibodies to well-known mitogenic factors. However, proliferation was significantly inhibited by the Wnt signaling antagonist, secreted frizzled related protein-1 (sFRP-1). In addition, anti-Wnt1 and anti-Wnt2 antibodies attenuated MSC-CM-induced proliferation, and increased expression of Wnt7b was identified. As would be expected in cells activated by Wnt, nuclear beta-catenin was increased. The amount of TGF-beta1 in MSC-CM and its biological activity were revealed by activation at acidic pH. The stem cells synthesized and released TGF-beta1 that increased alpha1-procollagen gene expression by LF target cells. Addition of anti-TGF-beta to the MSC-CM blocked upregulation of collagen gene expression. These data demonstrate that MSC from mice and humans produce Wnt proteins and TGF-beta1 that respectively stimulate LF proliferation and matrix production, two hallmarks of fibroproliferative lung disease. It will be essential to determine whether these factors can play a role in attempts to use MSC for therapeutic approaches.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/19734317
Author(s): Wynn TA, Ramalingam TR
Author(s): Sabry MM, Elkalawy SAE, Abo-Elnour RKE, Abd-El-Maksod DF
Author(s): Leung VYL, Aladin DMK, Lv F, Tam V, Sun Y, et al.
Author(s): Qi Y, Jiang D, Sindrilaru A, Stegemann A, Schatz S, et al.
Author(s): Kishore R, Verma SK, Mackie AR, Vaughan EE, Abramova TV, et al.
Author(s): Mias C, Lairez O, Trouche E, Roncalli J, Calise D, et al.
Author(s): Hemphill C, Stavoe K, Khalpey Z
Author(s): Zagoura DS, Roubelakis MG, Bitsika V, Trohatou O, Pappa KI, et al.
Author(s): Zhang DG, Jiang MY, Miao DS
Author(s): Fujimoto KL, Miki T, Liu LJ, Hashizume R, Strom SC, et al.
Author(s): Sedrakyan S, Da Sacco S, Milanesi A, Shiri L, Petrosyan A, et al.
Author(s): Garcia O, Carraro G, Turcatel G, Hall M, Sedrakyan S, et al.
Author(s): Sun D, Bu L, Liu C, Yin Z, Zhou X, et al.
Author(s): Wen ST, Chen W, Chen HL, Lai CW, Yen CC, et al.
Author(s): Baulier E, Favreau F, Le Corf A, Jayle C, Schneider F, et al.
Author(s): Lee WY, Wei HJ, Lin WW, Yeh YC, Hwang SM, et al.
Author(s): Grisafi D, Pozzobon M, Dedja A, Vanzo V, Tomanin R, et al.
Author(s): Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, et al.
Author(s): Cargnoni A, Piccinelli EC, Ressel L, Rossi D, Magatti M, et al.
Author(s): Cargnoni A, Ressel L, Rossi D, Poli A, Arienti D, et al.
Author(s): Wynn TA
Author(s): Klingberg F, Hinz B, White ES
Author(s): Yoon BS, Moon JH, Jun EK, Kim J, Maeng I, et al.
Author(s): Vosdoganes P, Wallace EM, Chan ST, Acharya R, Moss TJM, et al.
Author(s): Hodge A, Lourensz D, Vaghjiani V, Nguyen H, Tchongue J, et al.
Author(s): Jun EK, Zhang Q, Yoon BS, Moon JH, Lee G, et al.
Author(s): Fong CY, Tam K, Cheyyatraivendran S, Gan SU, Gauthaman K, et al.
Author(s): Arno AI, Amini-Nik S, Blit PH, Al-Shebab M, Belo C, et al.
Author(s): Jeon YK, Jang YH, Yoo DR, Kim SN, Lee SK, et al.
Author(s): Kim WS, Park BS, Sung JH, Yang JM, Park SB, et al.
Author(s): Jung H, Kim HH, Lee DH, Hwang YS, Yang HC, et al.
Author(s): Ding J, Ma Z, Shankowsky HA, Medina A, Tredget EE
Author(s): Lee SH, Jin SY, Song JS, Seo KK, Cho KH
Author(s): Onishi S, Sumiyoshi H, Kitamura S, Nagaya N
Author(s): Cho JW, Kang MC, Lee KS
Author(s): Leung A, Crombleholme TM, Keswani SG
Author(s): Hu MS, Rennert RC, McArdle A, Chung MT, Walmsley GG, et al.
Author(s): Hosper NA, Bank RA, van den Berg PP
Author(s): Przybyt E,Krenning G, Brinker MGL, Harmsen MC
Author(s): Masum MM, Boersema M, Bank RA
Author(s): Skardal A, Mack D, Kapetanovic E, Atala A, Jackson JD, et al.
Author(s): Shi HX, Lin C, Lin BB, Wang ZG, Zhang HY, et al.
Author(s): Kinoshita T, Ishikawa Y, Arita M, Akishima-Fukasawa Y, Fujita K, et al.
Author(s): Desai VD, Hsia HC, Schwatzbauer JE
Author(s): Murad S, Grove D, Lindberg KA, Reynolds G, Sivarajah A, et al.
Author(s): Pinnell SR
Author(s): Tsutsumi K, Fujikawa H, Kaijkawa T, Takedachi M, Yamamoto T, et al.
Author(s): Myllyharju J
Author(s): Ananthanarayanan VS
Author(s): Li Y, Schellhorn HE
Author(s): van der Slot AJ, Zuurmond A, Bardoel AFJ, Wijmenga C, Pruijs HEH, et al.
Author(s): Pornprasertsuk S, Duarte WR, Mochida Y, Yamauchi M
Author(s): van der Slot AJ, van Dura EA, Attema J, Blauw B, DeGroot J, et al.
Author(s): Mast BA, Diegelmann RF, Krummel TM, Cohen IK
Author(s): Longaker MT, Whitby DJ, Ferguson MWJ, Lorenz HP, Harrison MR, et al.