Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 1720 2023-06-29 23:33:10 |
2 format change + 1 word(s) 1721 2023-06-30 03:35:14 |

Video Upload Options

Do you have a full video?

Confirm

Are you sure to Delete?
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Nykänen, A.I.; Liu, M.; Keshavjee, S. Mesenchymal Stromal Cell Therapy in Lung Transplantation. Encyclopedia. Available online: https://encyclopedia.pub/entry/46244 (accessed on 18 April 2024).
Nykänen AI, Liu M, Keshavjee S. Mesenchymal Stromal Cell Therapy in Lung Transplantation. Encyclopedia. Available at: https://encyclopedia.pub/entry/46244. Accessed April 18, 2024.
Nykänen, Antti I., Mingyao Liu, Shaf Keshavjee. "Mesenchymal Stromal Cell Therapy in Lung Transplantation" Encyclopedia, https://encyclopedia.pub/entry/46244 (accessed April 18, 2024).
Nykänen, A.I., Liu, M., & Keshavjee, S. (2023, June 29). Mesenchymal Stromal Cell Therapy in Lung Transplantation. In Encyclopedia. https://encyclopedia.pub/entry/46244
Nykänen, Antti I., et al. "Mesenchymal Stromal Cell Therapy in Lung Transplantation." Encyclopedia. Web. 29 June, 2023.
Mesenchymal Stromal Cell Therapy in Lung Transplantation
Edit

Lung transplantation is often the only viable treatment option for a patient with end-stage lung disease. Lung transplant results have improved substantially over time, but ischemia-reperfusion injury, primary graft dysfunction, acute rejection, and chronic lung allograft dysfunction (CLAD) continue to be significant problems. Mesenchymal stromal cells (MSC) are pluripotent cells that have anti-inflammatory and protective paracrine effects and may be beneficial in solid organ transplantation. 

mesenchymal stromal cell lung transplantation cell therapy gene therapy ex vivo lung perfusion

1. Introduction

Lung transplantation is standard therapy for various end-stage lung diseases such as interstitial lung disease, obstructive lung disease, pulmonary hypertension, and cystic fibrosis. Almost 5000 lung transplants are reported annually in the International Society of Heart and Lung Transplantation Registry, and the results have improved over time [1]. However, the median survival of lung transplant recipients is limited to less than 7 years, and the main obstacles are primary graft dysfunction (PGD), acute rejection, chronic lung allograft dysfunction (CLAD), and side-effects of immunosuppressive drugs [2][3][4][5].
Mesenchymal stromal cells (MSC) are pluripotent cells present in most adult tissues [6][7]. MSC therapy in solid organ transplantation has gained attraction as MSCs possess anti-inflammatory, immunomodulatory, and protective features that could theoretically be utilized to counteract non-immunological and immunological injuries related to organ transplantation [8][9]. In lung transplantation, MSCs have been delivered in experimental studies to the donor lung to protect the transplant against ischemia-reperfusion injury (IRI) and PGD and to induce immunomodulatory effects [10]. In addition, small Phase 1 clinical trials have been performed in lung transplant patients with established CLAD [11][12][13], and additional clinical PGD and CLAD trials are ongoing [14].

2. Mesenchymal Stromal Cells

Mesenchymal stromal cells (MSC) and multipotent adult progenitor cells (MAPC) are mesenchymal, non-hematopoietic progenitor cells that are found in most tissues and are capable of self-renewal and differentiation into various types of stromal cells (Figure 1). Resident MSCs are also present in the lung, localized in perivascular spaces, where they act as important regulators of pulmonary homeostasis and the balance between lung injury and repair [15]. For therapeutic purposes, MSCs are commonly isolated from bone marrow, adipose tissue, the umbilical cord, and the placenta [6][7]. As considerable heterogeneity in cell sources, and isolation and expansion methods exist, the International Society for Cell Therapy has recommended minimal standard criteria to identify and characterize MSCs. Accordingly, MSCs should adhere to plastic in standard culture conditions, express typical stromal cell surface markers, lack expression of hematopoietic markers, and differentiate into osteoblasts, adipocytes, and chondroblasts in vitro under appropriate conditions [16]. While MAPCs resemble MCSs, they are biologically more primitive and have greater differentiation potential than classical MSCs [17].
Figure 1. Biological properties and effects of mesenchymal stromal cells. MSC are non-hematopoietic multipotent cells that have anti-inflammatory, immunomodulatory and protective effects mainly mediated though paracrine mechanisms.
Initially, MSCs and MAPCs were considered to result in cell replacement and renewal of damaged tissues; however, the current view is that the therapeutic effects of these cells are largely mediated by paracrine signaling, through the secretion of numerous soluble mediators, including growth factors, cytokines, and microRNA. This MSC secretome is considered to modulate inflammation and immune responses, and to stimulate innate tissue repair [6][18]. MSC therapies have been investigated in numerous clinical trials of cardiovascular disease, graft-versus host disease, and neurological disease, but the success has so far been variable [7]. Several studies have also examined the use of MSC in lung disease, especially in acute respiratory distress syndrome (ARDS) [19][20].

3. Lung Transplant MSC Therapy

The protective anti-inflammatory and immunomodulatory properties make MSCs attractive therapeutic candidates for lung transplantation. MSCs have been delivered to the lungs through the airways or intravascularly and can be administered into the donor lung either before transplantation or to the recipient before or after transplantation (Figure 2). Most of the preclinical studies have used MSCs to inhibit IRI, while some experiments have targeted acute rejection, and some clinical trials have explored MSC therapy in patients with CLAD (Table 1). Importantly, there is significant interaction between IRI, acute rejection, and CLAD (Figure 3), as lung injury may trigger alloimmune responses, and various non-immunological and immunological factors participate in the development of CLAD [5][21].
Figure 2. (A) MSC delivery routes to the lung transplant. MSC can be administered into the lungs through the airways with a flexible bronchoscope or intravascularly either intravenously, or directly through the pulmonary artery. (B) MSC administration can be performed before transplantation in situ in the donor or ex vivo during ex vivo lung perfusion, or after transplantation to the recipient.
Figure 3. MSC therapy targets in lung transplantation. (A) Lung transplant ischemia-reperfusion injury and primary graft dysfunction, (B) acute rejection and (C) chronic lung allograft dysfunction (CLAD) are potential targets for MSC therapy. In each lung transplant pathology, possible beneficial effects of MSCs are listed.
Table 1. Lung transplant and EVLP studies with MSCs.

Target

Species

Model

MSC

Administration

Effect

Ref

IRI

Rat

Lung hilar clamping

Engineered BM-MSC (MSC-vIL-10)

Intravenous

Improved oxygenation, inflammation and permeability

[22]

IRI

Pig

SLTx

BM-MSC

Pulmonary artery vs. endobronchial

Endobronchial MSC delivery improved lung compliance

[23]

IRI

Human

EVLP

MAPC

Airways

Decreased edema and inflammation

[24]

IRI

Human

EVLP

BM-MSC

Intravascular

Restored alveolar fluid clearance

[25]

IRI

Mouse

SLTx

BM-MSC

Recipient intravenous

Decreased IRI, MSC homing preferentially into the lung transplant

[26]

IRI

Pig

EVLP

UC-MSC

Airway vs. intravascular, 3 different doses

Intravascular delivery improved MSC lung retention, optimal dose 150 × 106 MSC decreased IL-8 and increased VEGF

[27]

IRI

Mouse

SLTx

BM-MSC

Ex vivo pulmonary artery

Decreased IRI

[28]

IRI

Pig

SLTx

BM-MSC

Pulmonary artery vs. endobronchial

No short-term differences detected

[29]

IRI

Mouse

Lung hilar clamping and EVLP

Human UC-MSC vs. MSC-EVs

Intravascular

MSCs and MSC-EVs attenuate IRI

[30]

IRI

Human

EVLP

MAPC

Airways

Decreased BAL neutrophilia, TNF-α, IL-1β and IFN-γ

[31]

IRI

Pig

SLTx

BM-MSC

Intravenous or intrabronchial

Heterogenous localization, in alveoli after endobronchial and in blood vessels after intravascular administration

[32]

IRI

Rat

SLTx

BM-MSC

Intravenous

Protection against IRI

[33]

IRI

Pig

EVLP and SLTx

UC-MSC

Intravascular

Decreased IRI during EVLP and after TX

[34]

IRI

Rat

EVLP

UC-MSC

Intravascular

Improved inflammation and IRI

[35]

IRI

Rat

EVLP

BM-MSC-EVs

Intravascular

Multiple influences on pulmonary energetics, tissue integrity and gene expression

[36]

IRI

Human

EVLP

Engineered UC-MSC (MSCIL−10)

Intravascular

Safe and feasible, results in rapid IL-10 elevation

[37]

IRI

Rat

SLTx

Donor vs. recipient adipose tissue MSC

Intravenous

MSCs, regardless of their origin, exert similar immunosuppressive effects

[38]

IRI/

ARDS

Human

EVLP/endotoxin

BM-MSC

Airways

Restored alveolar fluid clearance

[39]

IRI/

ARDS

Human

EVLP/e.coli pneumonia

BM-MSC

Airways

Restored alveolar fluid clearance, reduced inflammation and increased antimicrobial activity

[40]

Acute rejection

Rat

SLTx

BM-MSC

1 vs. 2 recipient intravenous doses

Protection from acute rejection, best result with 2 recipient doses

[41]

Acute rejection/

CLAD

Mouse

Ortotopic tracheal Tx

iPSC-MSC

Intravascular

Induces immune tolerance and supports long-term graft survival

[42]

CLAD

Mouse

Heterotopic tracheal Tx

MSC (various sources)

Intravenous

Prevents airway occlusion

[43]

CLAD

Mouse

Ortotopic tracheal Tx

BM-MSC

Intravenous

Prevents airway occlusion through macrophage cytokines

[44]

CLAD

Mouse

Heterotopic tracheal Tx

BM-MSC

Local vs. systemic vs. combination

Prevents airway occlusion through modulation of immune response, best effect with combination treatment

[45]

CLAD

Human

Clinical Tx

BM-MSC

Intravenous twice weekly for 2 weeks

Safe and feasible in patients with advanced CLAD

[13]

CLAD

Human

Clinical Tx

BM-MSC

Intravenous

Safe and feasible in patients with moderate CLAD

[12]

CLAD

Human

Clinical Tx

BM-MSC

Intravenous

Well tolerated in moderate-to-severe CLAD, low-dose may slow progression of CLAD in some patients

[11]

4. Strategies to Improve MSC Delivery and Therapeutic Potential

Although the lung is well accessible for MSC therapy with either airway or intravenous in vivo administration, cell delivery into an isolated donor lung during ex vivo lung perfusion (EVLP) would have several advantages.

4.1. MSC Delivery into the Donor Lung during EVLP

In EVLP, the isolated donor lung is perfused and ventilated in normothermia ex vivo (outside the body), enabling confirmation of donor lung quality before transplantation. This has revolutionized lung transplantation, as marginal donor lungs that would otherwise have been rejected from transplantation can be tested and transplanted if graft function is adequate [46]. A landmark clinical study evaluated high-risk donor lungs during EVLP and established that transplantation of lungs that were physiologically stable during 4 h of EVLP leads to post-transplant results similar to those obtained with conventionally selected lungs [47]. EVLP has safely and significantly increased the available pool of donor organs for transplantation, and later studies have shown that medium- and long-term lung transplant results remain excellent after EVLP evaluation [48][49].
EVLP has been used as a platform for cell therapy in several experimental studies using airway or intravascular delivery (Table 1). Mordant et al. compared different MSC doses and administration routes during pig lung EVLP. Intravascular administration resulted in better MSC retention in the lung, and most of the MSCs engraftment occurred within the first minutes after pulmonary artery injection [27]. Moreover, comparison of three different doses revealed that intravascular administration of 150 × 106 MSCs, the middle dose of the experiment, improved lung oxygenation and compliance. In contrast, a higher 300 × 106 MSCs dose temporarily increased pulmonary vascular resistance [27], possibly related to clustering of the cells into the lung microvasculature. These results highlight the efficacy of intravascular MSC delivery but also indicate that high cell doses may result in adverse embolic effects [27]. Interestingly, the optimal cell dose (150 × 106 MSCs; 5 × 106 per kg of animal weight) is close to the doses used in the clinical MSC CLAD studies [11][13][50]. In the studies administering MSCs during EVLP, decreased proinflammatory cytokine levels and protection of the alveolar-epithelial barrier function during ischemia- or endotoxin-induced lung injury have been observed [24][25][27][31][34][39][40]. Several studies have also reported that administration of MSC-derived EVs protects against lung injury [36][51].

4.2. Genetically Engineered MSCs

Genetic engineering of cell-based therapeutics with viral and non-viral vectors has been used to achieve modified cells with enhanced therapeutic properties. Genetic engineering modulates the MSC secretome and aims, for example, to enhance MSC migration to target sites, facilitate intrinsic repair properties, improve cell survival, or change MSCs into gene delivery vehicles [52].
Several different genetically modified MSCs have been studied in lung injury models, and for example, MSC engineered to produce anti-inflammatory IL-10 have been beneficial in lung IRI, endotoxemia, and ARDS [22][53][54]. In the recent study, the researchers transduced human umbilical cord-derived MSC with adenoviral vectors encoding IL-10 and administered these pre-modified and cryopreserved MSCIL−10 cells during EVLP to human lungs rejected from clinical transplantation. This rapidly elevated EVLP perfusate IL-10 levels in minutes, MSCIL−10 cells were retained in the lung, and IL-10 was increased also in lung tissue and the airway compartment [37]. While possible therapeutic or immunomodulatory effects of MSCIL−10 therapy are not known yet, these results indicate that therapy with genetically modified cells during standard clinical EVLP is feasible.

References

  1. Chambers, D.C.; Perch, M.; Zuckermann, A.; Cherikh, W.S.; Harhay, M.O.; HayesJr, D.; Hsich, E.; Khush, K.K.; Potena, L.; Sadavarte, A.; et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-eighth adult lung transplantation report—2021; Focus on recipient characteristics. J. Heart Lung Transpl. 2021, 40, 1060–1072.
  2. Chacon-Alberty, L.; Fernandez, R.; Jindra, P.; King, M.; Rosas, I.; Hochman-Mendez, C.; Loor, G. Primary Graft Dysfunction in Lung Transplantation: A Review of Mechanisms and Future Applications. Transplantation 2023.
  3. Parulekar, A.D.; Kao, C.C. Detection, classification, and management of rejection after lung transplantation. J. Thorac. Dis. 2019, 11, S1732–S1739.
  4. Ohm, B.; Jungraithmayr, W. B Cell Immunity in Lung Transplant Rejection—Effector Mechanisms and Therapeutic Implications. Front. Immunol. 2022, 13, 845867.
  5. Venado, A.; Kukreja, J.; Greenland, J.R. Chronic Lung Allograft Dysfunction. Thorac. Surg. Clin. 2022, 32, 231–242.
  6. Pittenger, M.F.; Discher, D.E.; Péault, B.M.; Phinney, D.G.; Hare, J.M.; Caplan, A.I. Mesenchymal stem cell perspective: Cell biology to clinical progress. npj Regen. Med. 2019, 4, 22.
  7. Galderisi, U.; Peluso, G.; Di Bernardo, G. Clinical Trials Based on Mesenchymal Stromal Cells are Exponentially Increasing: Where are We in Recent Years? Stem Cell Rev. Rep. 2022, 18, 23–36.
  8. Mansourabadi, A.H.; Mohamed Khosroshahi, L.; Noorbakhsh, F.; Amirzargar, A. Cell therapy in transplantation: A comprehensive review of the current applications of cell therapy in transplant patients with the focus on Tregs, CAR Tregs, and Mesenchymal stem cells. Int. Immunopharmacol. 2021, 97, 107669.
  9. Vandermeulen, M.; Erpicum, P.; Weekers, L.; Briquet, A.; Lechanteur, C.; Detry, O.; Beguin, Y.; Jouret, F. Mesenchymal Stromal Cells in Solid Organ Transplantation. Transplantation 2020, 104, 5.
  10. Miceli, V.; Bertani, A. Mesenchymal Stromal/Stem Cells and Their Products as a Therapeutic Tool to Advance Lung Transplantation. Cells 2022, 11, 826.
  11. Erasmus, D.B.; Durand, N.; Alvarez, F.A.; Narula, T.; Hodge, D.O.; Zubair, A.C. Feasibility and Safety of Low-Dose Mesenchymal Stem Cell Infusion in Lung Transplant Recipients. Stem Cells Transl. Med. 2022, 11, 891–899.
  12. Keller, C.A.; Gonwa, T.A.; Hodge, D.O.; Hei, D.J.; Centanni, J.M.; Zubair, A.C. Feasibility, Safety, and Tolerance of Mesenchymal Stem Cell Therapy for Obstructive Chronic Lung Allograft Dysfunction. Stem Cells Transl. Med. 2018, 7, 161–167.
  13. Chambers, D.C.; Enever, D.; Lawrence, S.; Sturm, M.J.; Herrmann, R.; Yerkovich, S.; Musk, M.; Hopkins, P.M. Mesenchymal Stromal Cell Therapy for Chronic Lung Allograft Dysfunction: Results of a First-in-Man Study. Stem Cells Transl. Med. 2017, 6, 1152–1157.
  14. Miller, C.L.; Jane, M.O.; Allan, J.S.; Madsen, J.C. Novel approaches for long-term lung transplant survival. Front. Immunol. 2022, 13, 931251.
  15. Doherty, D.F.; Roets, L.; Krasnodembskaya, A.D. The Role of Lung Resident Mesenchymal Stromal Cells in the Pathogenesis and Repair of Chronic Lung Disease. Stem Cells 2023, 41, 431–443.
  16. Dominici, M.; Le Blanc, K.; Mueller, I.; Slaper-Cortenbach, I.; Marini, F.; Krause, D.; Deans, R.; Keating, A.; Prockop, D.; Horwitz, E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006, 8, 315–317.
  17. Khan, R.S.; Newsome, P.N. A Comparison of Phenotypic and Functional Properties of Mesenchymal Stromal Cells and Multipotent Adult Progenitor Cells. Front. Immunol. 2019, 10, 1952.
  18. Han, Y.; Yang, J.; Fang, J.; Zhou, Y.; Candi, E.; Wang, J.; Hua, D.; Shao, C.; Shi, Y. The secretion profile of mesenchymal stem cells and potential applications in treating human diseases. Signal Transduct. Target. Ther. 2022, 7, 92.
  19. Wang, F.; Li, Y.; Wang, B.; Li, J.; Peng, Z. The safety and efficacy of mesenchymal stromal cells in ARDS: A meta-analysis of randomized controlled trials. Crit. Care 2023, 27, 31.
  20. Liu, A.; Zhang, X.; He, H.; Zhou, L.; Naito, Y.; Sugita, S.; Lee, J.W. Therapeutic potential of mesenchymal stem/stromal cell-derived secretome and vesicles for lung injury and disease. Expert Opin. Biol. Ther. 2020, 20, 125–140.
  21. Kawashima, M.; Juvet, S.C. The role of innate immunity in the long-term outcome of lung transplantation. Ann. Transl. Med. 2020, 8, 412.
  22. Manning, E.; Pham, S.; Li, S.; Vazquez-Padron, R.I.; Mathew, J.; Ruiz, P.; Salgar, S.K. Interleukin-10 delivery via mesenchymal stem cells: A novel gene therapy approach to prevent lung ischemia-reperfusion injury. Hum. Gene 2010, 21, 713–727.
  23. Wittwer, T.; Rahmanian, P.; Choi, Y.H.; Zeriouh, M.; Karavidic, S.; Neef, K.; Christmann, A.; Piatkowski, T.; Schnapper, A.; Ochs, M.; et al. Mesenchymal stem cell pretreatment of non-heart-beating-donors in experimental lung transplantation. J. Cardiothorac. Surg. 2014, 9, 151.
  24. La Francesca, S.; Ting, A.E.; Sakamoto, J.; Rhudy, J.; Bonenfant, N.R.; Borg, Z.D.; Cruz, F.F.; Goodwin, M.; Lehman, N.A.; Taggart, J.M.; et al. Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: An initial pilot and feasibility study. Transpl. Res. 2014, 3, 19.
  25. McAuley, D.F.; Curley, G.F.; Hamid, U.I.; Laffey, J.G.; Abbott, J.; McKenna, D.H.; Fang, X.; Matthay, M.A.; Lee, J.W. Clinical grade allogeneic human mesenchymal stem cells restore alveolar fluid clearance in human lungs rejected for transplantation. Am. J. Physiol. Lung Cell Mol. Physiol. 2014, 306, L809–L815.
  26. Tian, W.; Liu, Y.; Zhang, B.; Dai, X.; Li, G.; Li, X.; Zhang, Z.; Du, C.; Wang, H. Infusion of mesenchymal stem cells protects lung transplants from cold ischemia-reperfusion injury in mice. Lung 2015, 193, 85–95.
  27. Mordant, P.; Nakajima, D.; Kalaf, R.; Iskender, I.; Maahs, L.; Behrens, P.; Coutinho, R.; Iyer, R.K.; Davies, J.E.; Cypel, M.; et al. Mesenchymal stem cell treatment is associated with decreased perfusate concentration of interleukin-8 during ex vivo perfusion of donor lungs after 18-hour preservation. J. Heart Lung Transpl. 2016, 35, 1245–1254.
  28. Watanabe, T.; Hoshikawa, Y.; Ishibashi, N.; Suzuki, H.; Notsuda, H.; Watanabe, Y.; Noda, M.; Kanehira, M.; Ohkouchi, S.; Kondo, T.; et al. Mesenchymal stem cells attenuate ischemia-reperfusion injury after prolonged cold ischemia in a mouse model of lung transplantation: A preliminary study. Surg. Today 2017, 47, 425–431.
  29. Schnapper, A.; Christmann, A.; Knudsen, L.; Rahmanian, P.; Choi, Y.H.; Zeriouh, M.; Karavidic, S.; Neef, K.; Sterner-Kock, A.; Guschlbauer, M.; et al. Stereological assessment of the blood-air barrier and the surfactant system after mesenchymal stem cell pretreatment in a porcine non-heart-beating donor model for lung transplantation. J. Anat. 2018, 232, 283–295.
  30. Stone, M.L.; Zhao, Y.; Robert Smith, J.; Weiss, M.L.; Kron, I.L.; Laubach, V.E.; Sharma, A.K. Mesenchymal stromal cell-derived extracellular vesicles attenuate lung ischemia-reperfusion injury and enhance reconditioning of donor lungs after circulatory death. Respir. Res. 2017, 18, 212.
  31. Martens, A.; Ordies, S.; Vanaudenaerde, B.M.; Verleden, S.E.; Vos, R.; Van Raemdonck, D.E.; Verleden, G.M.; Roobrouck, V.D.; Claes, S.; Schols, D.; et al. Immunoregulatory effects of multipotent adult progenitor cells in a porcine ex vivo lung perfusion model. Stem Cell Res. 2017, 8, 159.
  32. Piatkowski, T.; Brandenberger, C.; Rahmanian, P.; Choi, Y.H.; Zeriouh, M.; Sabashnikov, A.; Wittwer, T.; Wahlers, T.C.W.; Ochs, M.; Mühlfeld, C. Localization of Exogenous Mesenchymal Stem Cells in a Pig Model of Lung Transplantation. Thorac. Cardiovasc. Surg. 2018, 66, 63–70.
  33. Wei, L.; Han, Z.J.; Xu, L.; Li, J.W. Effect of mesenchymal stem cells on expression of high mobility group box 1 protein in rats with ischemia reperfusion injury after lung transplantation. Zhonghua Yi Xue Za Zhi 2018, 98, 2019–2023.
  34. Nakajima, D.; Watanabe, Y.; Ohsumi, A.; Pipkin, M.; Chen, M.; Mordant, P.; Kanou, T.; Saito, T.; Lam, R.; Coutinho, R.; et al. Mesenchymal stromal cell therapy during ex vivo lung perfusion ameliorates ischemia-reperfusion injury in lung transplantation. J. Heart Lung Transpl. 2019, 38, 1214–1223.
  35. Pacienza, N.; Santa-Cruz, D.; Malvicini, R.; Robledo, O.; Lemus-Larralde, G.; Bertolotti, A.; Marcos, M.; Yannarelli, G. Mesenchymal Stem Cell Therapy Facilitates Donor Lung Preservation by Reducing Oxidative Damage during Ischemia. Stem Cells Int. 2019, 2019, 8089215.
  36. Lonati, C.; Bassani, G.A.; Brambilla, D.; Leonardi, P.; Carlin, A.; Maggioni, M.; Zanella, A.; Dondossola, D.; Fonsato, V.; Grange, C.; et al. Mesenchymal stem cell-derived extracellular vesicles improve the molecular phenotype of isolated rat lungs during ischemia/reperfusion injury. J. Heart Lung Transpl. 2019, 38, 1306–1316.
  37. Nykänen, A.I.; Mariscal, A.; Duong, A.; Estrada, C.; Ali, A.; Hough, O.; Sage, A.; Chao, B.T.; Chen, M.; Gokhale, H.; et al. Engineered mesenchymal stromal cell therapy during human lung ex vivo lung perfusion is compromised by acidic lung microenvironment. Mol. Methods Clin. Dev. 2021, 23, 184–197.
  38. Shimoyama, K.; Tsuchiya, T.; Watanabe, H.; Ergalad, A.; Iwatake, M.; Miyazaki, T.; Hashimoto, Y.; Hsu, Y.I.; Hatachi, G.; Matsumoto, K.; et al. Donor and Recipient Adipose-Derived Mesenchymal Stem Cell Therapy for Rat Lung Transplantation. Transpl. Proc. 2022, 54, 1998–2007.
  39. Lee, J.W.; Fang, X.; Gupta, N.; Serikov, V.; Matthay, M.A. Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc. Natl. Acad. Sci. USA 2009, 106, 16357–16362.
  40. Lee, J.W.; Krasnodembskaya, A.; McKenna, D.H.; Song, Y.; Abbott, J.; Matthay, M.A. Therapeutic effects of human mesenchymal stem cells in ex vivo human lungs injured with live bacteria. Am. J. Respir. Crit. Care Med. 2013, 187, 751–760.
  41. Ishibashi, N.; Watanabe, T.; Kanehira, M.; Watanabe, Y.; Hoshikawa, Y.; Notsuda, H.; Noda, M.; Sakurada, A.; Ohkouchi, S.; Kondo, T.; et al. Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis. Surg. Today 2018, 48, 726–734.
  42. Khan, M.A.; Alanazi, F.; Ahmed, H.A.; Shamma, T.; Kelly, K.; Hammad, M.A.; Alawad, A.O.; Assiri, A.M.; Broering, D.C. iPSC-derived MSC therapy induces immune tolerance and supports long-term graft survival in mouse orthotopic tracheal transplants. Stem Cell Res. 2019, 10, 290.
  43. Grove, D.A.; Xu, J.; Joodi, R.; Torres-Gonzales, E.; Neujahr, D.; Mora, A.L.; Rojas, M. Attenuation of early airway obstruction by mesenchymal stem cells in a murine model of heterotopic tracheal transplantation. J. Heart Lung Transpl. 2011, 30, 341–350.
  44. Guo, Z.; Zhou, X.; Li, J.; Meng, Q.; Cao, H.; Kang, L.; Ni, Y.; Fan, H.; Liu, Z. Mesenchymal stem cells reprogram host macrophages to attenuate obliterative bronchiolitis in murine orthotopic tracheal transplantation. Int. Immunopharmacol. 2013, 15, 726–734.
  45. Casey, A.; Dirks, F.; Liang, O.D.; Harrach, H.; Schuette-Nuetgen, K.; Leeman, K.; Kim, C.F.; Gerard, C.; Subramaniam, M. Bone marrow-derived multipotent stromal cells attenuate inflammation in obliterative airway disease in mouse tracheal allografts. Stem Cells Int. 2014, 2014, 468927.
  46. Watanabe, T.; Cypel, M.; Keshavjee, S. Ex vivo lung perfusion. J. Thorac. Dis. 2021, 13, 6602–6617.
  47. Cypel, M.; Yeung, J.C.; Liu, M.; Anraku, M.; Chen, F.; Karolak, W.; Sato, M.; Laratta, J.; Azad, S.; Madonik, M.; et al. Normothermic ex vivo lung perfusion in clinical lung transplantation. N. Engl. J. Med. 2011, 364, 1431–1440.
  48. Tikkanen, J.M.; Cypel, M.; Machuca, T.N.; Azad, S.; Binnie, M.; Chow, C.W.; Chaparro, C.; Hutcheon, M.; Yasufuku, K.; de Perrot, M.; et al. Functional outcomes and quality of life after normothermic ex vivo lung perfusion lung transplantation. J. Heart Lung Transpl. 2015, 34, 547–556.
  49. Divithotawela, C.; Cypel, M.; Martinu, T.; Singer, L.G.; Binnie, M.; Chow, C.W.; Chaparro, C.; Waddell, T.K.; de Perrot, M.; Pierre, A.; et al. Long-term Outcomes of Lung Transplant With Ex Vivo Lung Perfusion. JAMA Surg. 2019, 154, 1143–1150.
  50. Keller, M.; Bush, E.; Diamond, J.M.; Shah, P.; Matthew, J.; Brown, A.W.; Sun, J.; Timofte, I.; Kong, H.; Tunc, I.; et al. Use of donor-derived-cell-free DNA as a marker of early allograft injury in primary graft dysfunction (PGD) to predict the risk of chronic lung allograft dysfunction (CLAD). J. Heart Lung Transpl. 2021, 40, 488–493.
  51. Gennai, S.; Monsel, A.; Hao, Q.; Park, J.; Matthay, M.A.; Lee, J.W. Microvesicles Derived From Human Mesenchymal Stem Cells Restore Alveolar Fluid Clearance in Human Lungs Rejected for Transplantation. Am. J. Transpl. 2015, 15, 2404–2412.
  52. Damasceno, P.K.F.; de Santana, T.A.; Santos, G.C.; Orge, I.D.; Silva, D.N.; Albuquerque, J.F.; Golinelli, G.; Grisendi, G.; Pinelli, M.; Ribeiro dos Santos, R.; et al. Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine. Front. Cell Dev. Biol. 2020, 8, 737.
  53. Islam, D.; Huang, Y.; Fanelli, V.; Delsedime, L.; Wu, S.; Khang, J.; Han, B.; Grassi, A.; Li, M.; Xu, Y.; et al. Identification and Modulation of Microenvironment is Crucial for Effective MSC Therapy in Acute Lung Injury. Am. J. Respir. Crit. Care Med. 2019, 199, 1214–1224.
  54. Wang, C.; Lv, D.; Zhang, X.; Ni, Z.A.; Sun, X.; Zhu, C. Interleukin-10-Overexpressing Mesenchymal Stromal Cells Induce a Series of Regulatory Effects in the Inflammatory System and Promote the Survival of Endotoxin-Induced Acute Lung Injury in Mice Model. DNA Cell Biol. 2018, 37, 53–61.
More
Information
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : , ,
View Times: 196
Revisions: 2 times (View History)
Update Date: 30 Jun 2023
1000/1000