Lung-Derived Mesenchymal Stromal Cell Post-Transplantation Survival, Persistence, Paracrine Expression, and Repair of Elastase-Injured Lung
Publication: Stem Cells and Development
Volume 20, Issue Number 10
Abstract
While multipotent mesenchymal stromal cells have been recently isolated from adult lung (L-MSCs), there is very limited data on their biological properties and therapeutic potential in vivo. How L-MSCs compare with bone marrow-derived MSCs (BM-MSCs) is also unclear. In this study, we characterized L-MSC phenotype, clonogenicity, and differentiation potential, and compared L-MSCs to BM-MSCs in vivo survival, retention, paracrine gene expression, and repair or elastase injury after transplantation. L-MSCs were highly clonogenic, frequently expressed aldehyde dehydrogenase activity, and differentiated into osteocytes, chondrocytes, adipocytes, myofibroblasts, and smooth muscle cells. After intravenous injection (2 h), L-MSCs showed greater survival than BM-MSCs; similarly, L-MSCs were significantly more resistant than BM-MSCs to anchorage independent culture (4 h) in vitro. Long after transplantation (4 or 32 days), a significantly higher number of CD45neg L-MSCs were retained than BM-MSCs. By flow cytometry, L-MSCs expressed more intercellular adhesion molecule-1 (ICAM-1), platelet derived growth factor receptor alpha (PDGFRα), and integrin α2 than BM-MSCs; these proteins were found to modulate endothelial adherence, directional migration, and migration across Matrigel in L-MSCs. Further, L-MSCs with low ICAM-1 showed poorer lung retention and higher phagocytosis in vivo. Compared with BM-MSCs, L-MSCs expressed higher levels of several transcripts (e.g., Ccl2, Cxcl2, Cxcl10, IL-6, IL-11, Hgf, and Igf2) in vitro, although gene expression in vivo was increased by L-MSCs and BM-MSCs equivalently. Accordingly, both L-MSCs and BM-MSCs reduced elastase injury to the same extent. This study demonstrates that tissue-specific L-MSCs possess mechanisms that enhance their lung retention after intravenous transplantation, and produce substantial healing of elastase injury comparable to BM-MSCs.
Get full access to this article
View all available purchase options and get full access to this article.
References
1.
da Silva Meirelles LPC ChagastellesNB Nardi2006. Mesenchymal stem cells reside in virtually all post-natal organs and tissuesJ Cell Sci1192204-2213. 1. da Silva Meirelles L, PC Chagastelles and NB Nardi. (2006). Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 119:2204–2213.
2.
Weiss DJJK KollsLA OrtizA Panoskaltsis-MortariDJ Prockop2008. Stem cells and cell therapies in lung biology and lung diseasesProc Am Thorac Soc5637-667. 2. Weiss DJ, JK Kolls, LA Ortiz, A Panoskaltsis-Mortari and DJ Prockop. (2008). Stem cells and cell therapies in lung biology and lung diseases. Proc Am Thorac Soc 5:637–667.
3.
Matthay MAA GoolaertsJP HowardJW Lee2010. Mesenchymal stem cells for acute lung injury: preclinical evidenceCrit Care Med38S569-S573. 3. Matthay MA, A Goolaerts, JP Howard and JW Lee. (2010). Mesenchymal stem cells for acute lung injury: preclinical evidence. Crit Care Med 38:S569–S573.
4.
Zhen GZ XueJ ZhaoN GuZ TangY XuZ Zhang2010. Mesenchymal stem cell transplantation increases expression of vascular endothelial growth factor in papain-induced emphysematous lungs and inhibits apoptosis of lung cellsCytotherapy12605-614. 4. Zhen G, Z Xue, J Zhao, N Gu, Z Tang, Y Xu and Z Zhang. (2010). Mesenchymal stem cell transplantation increases expression of vascular endothelial growth factor in papain-induced emphysematous lungs and inhibits apoptosis of lung cells. Cytotherapy 12:605–614.
5.
Shigemura NM OkumuraS MizunoY ImanishiT NakamuraY Sawa2006. Autologous transplantation of adipose tissue-derived stromal cells ameliorates pulmonary emphysemaAm J Transplant62592-2600. 5. Shigemura N, M Okumura, S Mizuno, Y Imanishi, T Nakamura and Y Sawa. (2006). Autologous transplantation of adipose tissue-derived stromal cells ameliorates pulmonary emphysema. Am J Transplant 6:2592–2600.
6.
Ishizawa KH KuboM YamadaS KobayashiM NumasakiS UedaT SuzukiH Sasaki2004. Bone marrow-derived cells contribute to lung regeneration after elastase-induced pulmonary emphysemaFEBS Lett556249-252. 6. Ishizawa K, H Kubo, M Yamada, S Kobayashi, M Numasaki, S Ueda, T Suzuki and H Sasaki. (2004). Bone marrow-derived cells contribute to lung regeneration after elastase-induced pulmonary emphysema. FEBS Lett 556:249–252.
7.
Katsha AMS OhkouchiH XinM KanehiraR SunT NukiwaY Saijo2011. Paracrine factors of multipotent stromal cells ameliorate lung injury in an elastase-induced emphysema modelMol Ther19196-203. 7. Katsha AM, S Ohkouchi, H Xin, M Kanehira, R Sun, T Nukiwa and Y Saijo. (2011). Paracrine factors of multipotent stromal cells ameliorate lung injury in an elastase-induced emphysema model. Mol Ther 19:196–203.
8.
Nemeth KA LeelahavanichkulPS YuenB MayerA ParmeleeK DoiPG RobeyK LeelahavanichkulBH Koller et al.2009. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 productionNat Med1542-49. 8. Nemeth K, A Leelahavanichkul, PS Yuen, B Mayer, A Parmelee, K Doi, PG Robey, K Leelahavanichkul, BH Koller, et al. (2009). Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med 15:42–49.
9.
Xu JJ QuL CaoY SaiC ChenL HeL Yu2008. Mesenchymal stem cell-based angiopoietin-1 gene therapy for acute lung injury induced by lipopolysaccharide in miceJ Pathol214472-481. 9. Xu J, J Qu, L Cao, Y Sai, C Chen, L He and L Yu. (2008). Mesenchymal stem cell-based angiopoietin-1 gene therapy for acute lung injury induced by lipopolysaccharide in mice. J Pathol 214:472–481.
10.
Krasnodembskaya AY SongX FangN GuptaV SerikovJW LeeMA Matthay2010. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37Stem Cells282229-2238. 10. Krasnodembskaya A, Y Song, X Fang, N Gupta, V Serikov, JW Lee and MA Matthay. (2010). Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells 28:2229–2238.
11.
Serikov VBVM MikhaylovAD KrasnodembskayMA Matthay2008. Bone marrow-derived cells participate in stromal remodeling of the lung following acute bacterial pneumonia in miceLung186179-190. 11. Serikov VB, VM Mikhaylov, AD Krasnodembskay and MA Matthay. (2008). Bone marrow-derived cells participate in stromal remodeling of the lung following acute bacterial pneumonia in mice. Lung 186:179–190.
12.
van Haaften TR ByrneS BonnetGY RochefortJ AkabutuM BouchentoufGJ Rey-ParraJ GalipeauA Haromy et al.2009. Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in ratsAm J Respir Crit Care Med1801131-1142. 12. van Haaften T, R Byrne, S Bonnet, GY Rochefort, J Akabutu, M Bouchentouf, GJ Rey-Parra, J Galipeau, A Haromy, et al. (2009). Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in rats. Am J Respir Crit Care Med 180:1131–1142.
13.
Aslam MR BavejaOD LiangA Fernandez-GonzalezC LeeSA MitsialisS Kourembanas2009. Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung diseaseAm J Respir Crit Care Med1801122-1130. 13. Aslam M, R Baveja, OD Liang, A Fernandez-Gonzalez, C Lee, SA Mitsialis and S Kourembanas. (2009). Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease. Am J Respir Crit Care Med 180:1122–1130.
14.
Fritzell JA Jr.Q MaoS GundavarapuT PasquarielloJM AliottaA AyalaJF PadburyME De Paepe2009. Fate and effects of adult bone marrow cells in lungs of normoxic and hyperoxic newborn miceAm J Respir Cell Mol Biol40575-587. 14. Fritzell JA Jr., Q Mao, S Gundavarapu, T Pasquariello, JM Aliotta, A Ayala, JF Padbury and ME De Paepe. (2009). Fate and effects of adult bone marrow cells in lungs of normoxic and hyperoxic newborn mice. Am J Respir Cell Mol Biol 40:575–587.
15.
Tian ZFJ DuXM FuB WangXY HongZC Feng2008. Influence of human bone marrow-derived mesenchymal stem cells on the lung of newborn rats damaged by hyperoxiaZhonghua Er Ke Za Zhi464-8. 15. Tian ZF, J Du, XM Fu, B Wang, XY Hong and ZC Feng. (2008). Influence of human bone marrow-derived mesenchymal stem cells on the lung of newborn rats damaged by hyperoxia. Zhonghua Er Ke Za Zhi 46:4–8.
16.
Tian ZFJ DuB WangXY HongZC Feng2007. Intravenous infusion of rat bone marrow-derived mesenchymal stem cells ameliorates hyperoxia-induced lung injury in neonatal ratsNan Fang Yi Ke Da Xue Xue Bao271692-1695. 16. Tian ZF, J Du, B Wang, XY Hong and ZC Feng. (2007). Intravenous infusion of rat bone marrow-derived mesenchymal stem cells ameliorates hyperoxia-induced lung injury in neonatal rats. Nan Fang Yi Ke Da Xue Xue Bao 27:1692–1695.
17.
Irwin DK HelmN CampbellM ImamuraK FaganJ HarralM CarrKA YoungD Klemm et al.2007. Neonatal lung side population cells demonstrate endothelial potential and are altered in response to hyperoxia-induced lung simplificationAm J Physiol Lung Cell Mol Physiol293L941-L951. 17. Irwin D, K Helm, N Campbell, M Imamura, K Fagan, J Harral, M Carr, KA Young, D Klemm, et al. (2007). Neonatal lung side population cells demonstrate endothelial potential and are altered in response to hyperoxia-induced lung simplification. Am J Physiol Lung Cell Mol Physiol 293:L941–L951.
18.
Lee SHAS JangYE KimJY ChaTH KimS JungSK ParkYK LeeJH WonYH KimCS Park2010. Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosisRespir Res1116. 18. Lee SH, AS Jang, YE Kim, JY Cha, TH Kim, S Jung, SK Park, YK Lee, JH Won, YH Kim and CS Park. (2010). Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis. Respir Res 11:16.
19.
Xu JET GonzalezSS IyerV MacAL MoraRL SutliffA ReedKL BrighamP KellyM Rojas2009. Use of senescence-accelerated mouse model in bleomycin-induced lung injury suggests that bone marrow-derived cells can alter the outcome of lung injury in aged miceJ Gerontol A Biol Sci Med Sci64731-739. 19. Xu J, ET Gonzalez, SS Iyer, V Mac, AL Mora, RL Sutliff, A Reed, KL Brigham, P Kelly and M Rojas. (2009). Use of senescence-accelerated mouse model in bleomycin-induced lung injury suggests that bone marrow-derived cells can alter the outcome of lung injury in aged mice. J Gerontol A Biol Sci Med Sci 64:731–739.
20.
Liebler JMC LutzkoA BanfalviD SenadheeraN AghamohammadiED CrandallZ Borok2008. Retention of human bone marrow-derived cells in murine lungs following bleomycin-induced lung injuryAm J Physiol Lung Cell Mol Physiol295L285-L292. 20. Liebler JM, C Lutzko, A Banfalvi, D Senadheera, N Aghamohammadi, ED Crandall and Z Borok. (2008). Retention of human bone marrow-derived cells in murine lungs following bleomycin-induced lung injury. Am J Physiol Lung Cell Mol Physiol 295:L285–L292.
21.
Cui AHP DaiJW DaiBS PangSJ NiuYP LuC Wang2007. Effects of bone marrow mesenchymal stem cells on bleomycin induced pulmonary fibrosis in ratsZhonghua Jie He He Hu Xi Za Zhi30677-682. 21. Cui A, HP Dai, JW Dai, BS Pang, SJ Niu, YP Lu and C Wang. (2007). Effects of bone marrow mesenchymal stem cells on bleomycin induced pulmonary fibrosis in rats. Zhonghua Jie He He Hu Xi Za Zhi 30:677–682.
22.
Ortiz LAF GambelliC McBrideD GauppM BaddooN KaminskiDG Phinney2003. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effectsProc Natl Acad Sci USA1008407-8411. 22. Ortiz LA, F Gambelli, C McBride, D Gaupp, M Baddoo, N Kaminski and DG Phinney. (2003). Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci USA 100:8407–8411.
23.
McQualter JLN BrouardB WilliamsBN BairdS Sims-LucasK YuenSK NilssonPJ SimmonsI Bertoncello2009. Endogenous fibroblastic progenitor cells in the adult mouse lung are highly enriched in the sca-1 positive cell fractionStem Cells27623-633. 23. McQualter JL, N Brouard, B Williams, BN Baird, S Sims-Lucas, K Yuen, SK Nilsson, PJ Simmons and I Bertoncello. (2009). Endogenous fibroblastic progenitor cells in the adult mouse lung are highly enriched in the sca-1 positive cell fraction. Stem Cells 27:623–633.
24.
Summer RK FitzsimmonsD DwyerJ MurphyA Fine2007. Isolation of an adult mouse lung mesenchymal progenitor cell populationAm J Respir Cell Mol Biol37152-159. 24. Summer R, K Fitzsimmons, D Dwyer, J Murphy and A Fine. (2007). Isolation of an adult mouse lung mesenchymal progenitor cell population. Am J Respir Cell Mol Biol 37:152–159.
25.
Hegab AEH KuboN FujinoT SuzukiM HeH KatoM Yamaya2010. Isolation and characterization of murine multipotent lung stem cellsStem Cells Dev19523-536. 25. Hegab AE, H Kubo, N Fujino, T Suzuki, M He, H Kato and M Yamaya. (2010). Isolation and characterization of murine multipotent lung stem cells. Stem Cells Dev 19:523–536.
26.
Reynolds SDH ShenPR ReynoldsT BetsuyakuJM PilewskiF GambelliM DeGuiseppeLA OrtizBR Stripp2007. Molecular and functional properties of lung SP cellsAm J Physiol Lung Cell Mol Physiol292L972-L983. 26. Reynolds SD, H Shen, PR Reynolds, T Betsuyaku, JM Pilewski, F Gambelli, M DeGuiseppe, LA Ortiz and BR Stripp. (2007). Molecular and functional properties of lung SP cells. Am J Physiol Lung Cell Mol Physiol 292:L972–L983.
27.
Martin JK HelmP RueggM Varella-GarciaE BurnhamS Majka2008. Adult lung side population cells have mesenchymal stem cell potentialCytotherapy10140-151. 27. Martin J, K Helm, P Ruegg, M Varella-Garcia, E Burnham and S Majka. (2008). Adult lung side population cells have mesenchymal stem cell potential. Cytotherapy 10:140–151.
28.
Jarvinen LL BadriS WettlauferT OhtsukaTJ StandifordGB ToewsDJ PinskyM Peters-GoldenVN Lama2008. Lung resident mesenchymal stem cells isolated from human lung allografts inhibit T cell proliferation via a soluble mediatorJ Immunol1814389-4396. 28. Jarvinen L, L Badri, S Wettlaufer, T Ohtsuka, TJ Standiford, GB Toews, DJ Pinsky, M Peters-Golden and VN Lama. (2008). Lung resident mesenchymal stem cells isolated from human lung allografts inhibit T cell proliferation via a soluble mediator. J Immunol 181:4389–4396.
29.
Lama VNL SmithL BadriA FlintAC AndreiS MurrayZ WangH LiaoGB Toews et al.2007. Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allograftsJ Clin Invest117989-996. 29. Lama VN, L Smith, L Badri, A Flint, AC Andrei, S Murray, Z Wang, H Liao, GB Toews, et al. (2007). Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts. J Clin Invest 117:989–996.
30.
Hennrick KTAG KeetonS NanuaTG KijekAM GoldsmithUS SajjanJK BentleyVN LamaBB Moore et al.2007. Lung cells from neonates show a mesenchymal stem cell phenotypeAm J Respir Crit Care Med1751158-1164. 30. Hennrick KT, AG Keeton, S Nanua, TG Kijek, AM Goldsmith, US Sajjan, JK Bentley, VN Lama, BB Moore, et al. (2007). Lung cells from neonates show a mesenchymal stem cell phenotype. Am J Respir Crit Care Med 175:1158–1164.
31.
Ingenito EPE SenLW TsaiS MurthyA Hoffman2010. Design and testing of biological scaffolds for delivering reparative cells to target sites in the lungJ Tissue Eng Regen Med4259-272. 31. Ingenito EP, E Sen, LW Tsai, S Murthy and A Hoffman. (2010). Design and testing of biological scaffolds for delivering reparative cells to target sites in the lung. J Tissue Eng Regen Med 4:259–272.
32.
Ingenito EPL TsaiS MurthyS TyagiM MazanA Hoffman2011. Autologous lung-derived mesenchymal stem cell transplantation in experimental emphysemaCell Transplant. 32. Ingenito EP, L Tsai, S Murthy, S Tyagi, M Mazan and A Hoffman. (2011). Autologous lung-derived mesenchymal stem cell transplantation in experimental emphysema. Cell Transplant DOI: 10.3727/096368910X550233.
33.
Summer RA Fine2008. Mesenchymal progenitor cell research: limitations and recommendationsProc Am Thorac Soc5707-710. 33. Summer R and A Fine. (2008). Mesenchymal progenitor cell research: limitations and recommendations. Proc Am Thorac Soc 5:707–710.
34.
Jun DHC GaratJ WestN ThornKS ChowT CleaverT SullivanEC TorchiaC Childs et al.2011. The pathology of bleomycin induced fibrosis is associated with loss of resident lung mesenchymal stem cells which regulate effector t-cell proliferationStem Cells29725-735. 34. Jun DH, C Garat, J West, N Thorn, KS Chow, T Cleaver, T Sullivan, EC Torchia, C Childs, et al. (2011). The pathology of bleomycin induced fibrosis is associated with loss of resident lung mesenchymal stem cells which regulate effector t-cell proliferation. Stem Cells 29:725–735.
35.
Ingenito EPE SenLW TsaiS MurthyA Hoffman2009. Design and testing of biological scaffolds for delivering reparative cells to target sites in the lungJ Tissue Eng Regen Med4259-272. 35. Ingenito EP, E Sen, LW Tsai, S Murthy and A Hoffman. (2009). Design and testing of biological scaffolds for delivering reparative cells to target sites in the lung. J Tissue Eng Regen Med 4:259–272.
36.
Hoffman AMA ShifrenMR MazanAM GruntmanKM LascolaRD Nolen-WalstonCF KimL TsaiRA PierceRP MechamEP Ingenito2010. Matrix modulation of compensatory lung regrowth and progenitor cell proliferation in miceAm J Physiol Lung Cell Mol Physiol298L158-L168. 36. Hoffman AM, A Shifren, MR Mazan, AM Gruntman, KM Lascola, RD Nolen-Walston, CF Kim, L Tsai, RA Pierce, RP Mecham and EP Ingenito. (2010). Matrix modulation of compensatory lung regrowth and progenitor cell proliferation in mice. Am J Physiol Lung Cell Mol Physiol 298:L158–L168.
37.
Paxson JACD ParkinLK IyerMR MazanEP IngenitoAM Hoffman2009. Global gene expression patterns in the post-pneumonectomy lung of adult miceRespir Res1092. 37. Paxson JA, CD Parkin, LK Iyer, MR Mazan, EP Ingenito and AM Hoffman. (2009). Global gene expression patterns in the post-pneumonectomy lung of adult mice. Respir Res 10:92.
38.
Pfaffl MW2001. A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Res29e45. 38. Pfaffl MW. (2001). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45.
39.
Xouri GS Christian2010. Origin and function of tumor stroma fibroblastsSemin Cell Dev Biol2140-46. 39. Xouri G and S Christian. (2010). Origin and function of tumor stroma fibroblasts. Semin Cell Dev Biol 21:40–46.
40.
Sabeh FXY LiTL SaundersRG RoweSJ Weiss2009. Secreted versus membrane-anchored collagenases: relative roles in fibroblast-dependent collagenolysis and invasionJ Biol Chem28423001-23011. 40. Sabeh F, XY Li, TL Saunders, RG Rowe and SJ Weiss. (2009). Secreted versus membrane-anchored collagenases: relative roles in fibroblast-dependent collagenolysis and invasion. J Biol Chem 284:23001–23011.
41.
Haniffa MAMP CollinCD BuckleyF Dazzi2009. Mesenchymal stem cells: the fibroblasts' new clothes?Haematologica94258-263. 41. Haniffa MA, MP Collin, CD Buckley and F Dazzi. (2009). Mesenchymal stem cells: the fibroblasts' new clothes? Haematologica 94:258–263.
42.
Haniffa MAXN WangU HoltickM RaeJD IsaacsAM DickinsonCM HilkensMP Collin2007. Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cellsJ Immunol1791595-1604. 42. Haniffa MA, XN Wang, U Holtick, M Rae, JD Isaacs, AM Dickinson, CM Hilkens and MP Collin. (2007). Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cells. J Immunol 179:1595–1604.
43.
Sabatini FL PetecchiaM TavianV Jodon de VillerocheGA RossiD Brouty-Boye2005. Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialitiesLab Invest85962-971. 43. Sabatini F, L Petecchia, M Tavian, V Jodon de Villeroche, GA Rossi and D Brouty-Boye. (2005). Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. Lab Invest 85:962–971.
44.
McQualter JLN BrouardB WilliamsBN BairdS Sims-LucasK YuenSK NilssonPJ SimmonsI Bertoncello2009. Endogenous fibroblastic progenitor cells in the adult mouse lung are highly enriched in the Sca-1 positive cell fractionStem Cells27623-633. 44. McQualter JL, N Brouard, B Williams, BN Baird, S Sims-Lucas, K Yuen, SK Nilsson, PJ Simmons and I Bertoncello. (2009). Endogenous fibroblastic progenitor cells in the adult mouse lung are highly enriched in the Sca-1 positive cell fraction. Stem Cells 27:623–633.
45.
Weiss DJMA BerberichZ BorokDB GailJK KollsC PenlandDJ Prockop2006. Adult stem cells, lung biology, and lung disease. NHLBI/Cystic Fibrosis Foundation WorkshopProc Am Thorac Soc3193-207. 45. Weiss DJ, MA Berberich, Z Borok, DB Gail, JK Kolls, C Penland and DJ Prockop. (2006). Adult stem cells, lung biology, and lung disease. NHLBI/Cystic Fibrosis Foundation Workshop. Proc Am Thorac Soc 3:193–207.
46.
Hayflick L1965. The limited in vitro lifetime of human diploid cell strainsExp Cell Res37614-636. 46. Hayflick L. (1965). The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636.
47.
Balber AE2011. ALDH bright stem and progenitor cell populations from normal tissues: characteristics, activities and emerging uses in regenerative medicineStem Cells29570-575. 47. Balber AE. (2011). ALDH bright stem and progenitor cell populations from normal tissues: characteristics, activities and emerging uses in regenerative medicine. Stem Cells 29:570–575.
48.
Lee CHB ShahEK MoioliJJ Mao2010. CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells and defines connective tissue healing in a rodent injury modelJ Clin Invest1203340-3349. 48. Lee CH, B Shah, EK Moioli and JJ Mao. (2010). CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells and defines connective tissue healing in a rodent injury model. J Clin Invest 120:3340–3349.
49.
Petersen THEA CalleL ZhaoEJ LeeL GuiMB RaredonK GavrilovT YiZW Zhuang et al.2010. Tissue-engineered lungs for in vivo implantationScience329538-541. 49. Petersen TH, EA Calle, L Zhao, EJ Lee, L Gui, MB Raredon, K Gavrilov, T Yi, ZW Zhuang, et al. (2010). Tissue-engineered lungs for in vivo implantation. Science 329:538–541.
50.
Cortiella JJ NilesA CantuA BrettlerA PhamG VargasS WinstonJ WangS WallsJE Nichols2010. Influence of acellular natural lung matrix on murine embryonic stem cell differentiation and tissue formationTissue Eng Part A162565-2580. 50. Cortiella J, J Niles, A Cantu, A Brettler, A Pham, G Vargas, S Winston, J Wang, S Walls and JE Nichols. (2010). Influence of acellular natural lung matrix on murine embryonic stem cell differentiation and tissue formation. Tissue Eng Part A 16:2565–2580.
51.
Karp JMGS Leng Teo2009. Mesenchymal stem cell homing: the devil is in the detailsCell Stem Cell4206-216. 51. Karp JM and GS Leng Teo. (2009). Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell 4:206–216.
52.
Sordi V2009. Mesenchymal stem cell homing capacityTransplantation87S42-S45. 52. Sordi V. (2009). Mesenchymal stem cell homing capacity. Transplantation 87:S42–S45.
53.
Lochter AM NavreZ WerbMJ Bissell1999. alpha1 and alpha2 integrins mediate invasive activity of mouse mammary carcinoma cells through regulation of stromelysin-1 expressionMol Biol Cell10271-282. 53. Lochter A, M Navre, Z Werb and MJ Bissell. (1999). alpha1 and alpha2 integrins mediate invasive activity of mouse mammary carcinoma cells through regulation of stromelysin-1 expression. Mol Biol Cell 10:271–282.
54.
Pankov RY EndoS Even-RamM ArakiK ClarkE CukiermanK MatsumotoKM Yamada2005. A Rac switch regulates random versus directionally persistent cell migrationJ Cell Biol170793-802. 54. Pankov R, Y Endo, S Even-Ram, M Araki, K Clark, E Cukierman, K Matsumoto and KM Yamada. (2005). A Rac switch regulates random versus directionally persistent cell migration. J Cell Biol 170:793–802.
55.
Schmidt SP Friedl2010. Interstitial cell migration: integrin-dependent and alternative adhesion mechanismsCell Tissue Res33983-92. 55. Schmidt S and P Friedl. (2010). Interstitial cell migration: integrin-dependent and alternative adhesion mechanisms. Cell Tissue Res 339:83–92.
56.
Kollar KMM CookK AtkinsonG Brooke2009. Molecular mechanisms involved in mesenchymal stem cell migration to the site of acute myocardial infarctionInt J Cell Biol2009904682. 56. Kollar K, MM Cook, K Atkinson and G Brooke. (2009). Molecular mechanisms involved in mesenchymal stem cell migration to the site of acute myocardial infarction. Int J Cell Biol 2009:904682.
57.
Petrie RJAD DoyleKM Yamada2009. Random versus directionally persistent cell migrationNat Rev Mol Cell Biol10538-549. 57. Petrie RJ, AD Doyle and KM Yamada. (2009). Random versus directionally persistent cell migration. Nat Rev Mol Cell Biol 10:538–549.
58.
Epting CLJE LopezA PedersenC BrownP SpitzPC UrsellHS Bernstein2008. Stem cell antigen-1 regulates the tempo of muscle repair through effects on proliferation of alpha7 integrin-expressing myoblastsExp Cell Res3141125-1135. 58. Epting CL, JE Lopez, A Pedersen, C Brown, P Spitz, PC Ursell and HS Bernstein. (2008). Stem cell antigen-1 regulates the tempo of muscle repair through effects on proliferation of alpha7 integrin-expressing myoblasts. Exp Cell Res 314:1125–1135.
59.
Sudo KY YamadaK SaitoS ShimizuH OhashiT KatoH MoriwakiH ItoM Seishima2008. TNF-alpha and IL-6 signals from the bone marrow derived cells are necessary for normal murine liver regenerationBiochim Biophys Acta1782671-679. 59. Sudo K, Y Yamada, K Saito, S Shimizu, H Ohashi, T Kato, H Moriwaki, H Ito and M Seishima. (2008). TNF-alpha and IL-6 signals from the bone marrow derived cells are necessary for normal murine liver regeneration. Biochim Biophys Acta 1782:671–679.
60.
Pachowka MJ ZegarskaR CiecierskiG Korczak-Kowalska2008. The role of IL-6 during the late phase of liver regenerationAnn Transplant1315-19. 60. Pachowka M, J Zegarska, R Ciecierski and G Korczak-Kowalska. (2008). The role of IL-6 during the late phase of liver regeneration. Ann Transplant 13:15–19.
61.
Nechemia-Arbely YA ShrikiU DenzC DruckerJ SchellerJ RaubO PappoS Rose-JohnE GalunJH Axelrod2011. Early hepatocyte DNA synthetic response posthepatectomy is modulated by IL-6 trans-signaling and PI3K/AKT activationJ Hepatol54922-929. 61. Nechemia-Arbely Y, A Shriki, U Denz, C Drucker, J Scheller, J Raub, O Pappo, S Rose-John, E Galun and JH Axelrod. (2011). Early hepatocyte DNA synthetic response posthepatectomy is modulated by IL-6 trans-signaling and PI3K/AKT activation. J Hepatol 54:922–929.
62.
Sun RB JarugaS KulkarniH SunB Gao2005. IL-6 modulates hepatocyte proliferation via induction of HGF/p21cip1: regulation by SOCS3Biochem Biophys Res Commun3381943-1949. 62. Sun R, B Jaruga, S Kulkarni, H Sun and B Gao. (2005). IL-6 modulates hepatocyte proliferation via induction of HGF/p21cip1: regulation by SOCS3. Biochem Biophys Res Commun 338:1943–1949.
63.
Cai LBH JohnstoneTG CookZ LiangD TraktuevK CornettaDA IngramED RosenKL March2007. Suppression of hepatocyte growth factor production impairs the ability of adipose-derived stem cells to promote ischemic tissue revascularizationStem Cells253234-3243. 63. Cai L, BH Johnstone, TG Cook, Z Liang, D Traktuev, K Cornetta, DA Ingram, ED Rosen and KL March. (2007). Suppression of hepatocyte growth factor production impairs the ability of adipose-derived stem cells to promote ischemic tissue revascularization. Stem Cells 25:3234–3243.
64.
Matthay MABT ThompsonEJ ReadDH McKenna Jr.KD LiuCS CalfeeJW Lee2010. Therapeutic potential of mesenchymal stem cells for severe acute lung injuryChest138965-972. 64. Matthay MA, BT Thompson, EJ Read, DH McKenna Jr., KD Liu, CS Calfee and JW Lee. (2010). Therapeutic potential of mesenchymal stem cells for severe acute lung injury. Chest 138:965–972.
Information & Authors
Information
Published In
Stem Cells and Development
Volume 20 • Issue Number 10 • October 2011
Pages: 1779 - 1792
PubMed: 21585237
Copyright
Copyright 2011, Mary Ann Liebert, Inc.
History
Published in print: October 2011
Published ahead of print: 6 July 2011
Published online: 17 May 2011
Accepted: 13 May 2011
Received: 6 March 2011
Topics
Authors
Author Disclosure Statement
The authors have no financial disclosure to declare.
Metrics & Citations
Metrics
Citations
Export Citation
Export citation
Select the format you want to export the citations of this publication.
View Options
Get Access
Access content
To read the fulltext, please use one of the options below to sign in or purchase access.⚠ Society Access
If you are a member of a society that has access to this content please log in via your society website and then return to this publication.