Translational lung transplantation and lung cell therapy research

Our Research

The Lindstedt group is led by Professor Sandra Lindstedt, a senior consultant in thoracic surgery specializing in heart and lung transplantation, with a long-standing interest in lung transplantation related research, post-transplant complications and lung regeneration.

Lung transplantation (LTx) is the only effective treatment for patients with end stage lung disease. Over 64,000 lung transplants have been performed worldwide, with over 4,500 being conducted annually. Despite improvements in the transplant procedure, ischemia-reperfusion (IR) induced lung injury remains the leading cause of primary graft dysfunction (PGD), early recipient mortality, and contributes to the development of chronic lung allograft dysfunction (CLAD). Fear of these complications leads to low utilization rate (approximately 25%) of donated lungs.

A reason for rejecting a donated lung is lung injuries caused by processes such as acute respiratory distress syndrome (ARDS). Consequently, new potential therapies are being explored to treat lung injuries in patients with ARDS to improve outcome and in organ donors to improve the availability and quality of suitable donor organs.

The Lindstedt group has created ex vivo human models and in vivo and ex vivo porcine models of lung injuries such as ARDS, the broad category of respiratory disease for severe COVID-19 patients. The Lindstedt group are currently working to develop mesenchymal stromal cell therapies within these models. Interested in pursuing this research with ARDS, as well as other settings of lung regeneration following lung injury such as PGD, with the aim to treat ARDS and to increase the number of lungs suitable for transplantation but also to reduce complications after lung transplantation by increasing the tolerability of the new organ and bring this research towards clinical applications.

Aims

• Translational and clinical approaches to develop novel therapeutic treatments for lung injury
• Evaluating treatments such as cell therapy in ARDS, Ex Vivo Lung Perfusion (EVLP), Extra corporal membrane oxygenation (ECMO), PGD and transplant models and its effectiveness of reducing inflammatory mediators and immune response
• Increase the number of lungs suitable for transplantation but also to reduce complications after lung transplantation by increasing the tolerability of the new organ
• Bring cell therapy into clinical applications

Impact

The need for lung transplantation radically exceeds the availability of organs resulting in deaths on the waiting list. In addition, 85% of donor grafts are unused due to lung injury. Methods to increase the number of donor organs and their quality is therefore crucial. Additionally, when a donor organ is transplanted, survival remains low due to the development of PGD and CLAD. There is a general lack of treatments for both PGD and CLAD. Furthermore, ARDS is a common cause of death in the intensive care unit with mortality rates of around 30-50% and even up to 80% in COVID-19-induced ARDS patients. There is currently no approved therapy for ARDS, other than supportive interventions, such as ventilatory and circulatory support. MSCs and its derivatives constitutes a potential treatment for inflammatory states in the lung and may also potentially offer support after transplantation, due to their anti-inflammatory and immunomodulatory effect.

List of team Lindstedt publications

Team

Sandra Lindstedt

Principal Investigator, Sandra [dot] Lindstedt [at] med [dot] lu [dot] se (Sandra[dot]Lindstedt[at]med[dot]lu[dot]se)

Franziska Olm

Postdoc, Franziska [dot] Olm [at] med [dot] lu [dot] se (Franziska[dot]Olm[at]med[dot]lu[dot]se)

Nicholas Bèchet

Postdoc, nicholas [dot] bechet [at] med [dot] lu [dot] se (nicholas[dot]bechet[at]med[dot]lu[dot]se)

Anna Niroomand

Postdoc, an608 [at] rwjms [dot] rutgers [dot] edu (an608[at]rwjms[dot]rutgers[dot]edu)

Aybüke Celik

Postdoc, aybuke [dot] celik [at] med [dot] lu [dot] se (aybuke[dot]celik[at]med[dot]lu[dot]se)

Margareta Mittendorfer

PhD Student, Margareta [dot] Mittendorfer [at] med [dot] lu [dot] se (Margareta[dot]Mittendorfer[at]med[dot]lu[dot]se)

Jesper Andreasson

PhD Student, Jesper [dot] Andreasson [at] skane [dot] se (Jesper[dot]Andreasson[at]skane[dot]se)

Embla Bodén Janson

PhD student, Embla [dot] Boden_Janson [at] med [dot] lu [dot] se (Embla[dot]Boden_Janson[at]med[dot]lu[dot]se)

Dag Edström

PhD Student, Dag [dot] Edstrom [at] med [dot] lu [dot] se (Dag[dot]Edstrom[at]med[dot]lu[dot]se)

Gabriel Hirdman

PhD Student, Gabriel [dot] Hirdman [at] med [dot] lu [dot] se (Gabriel[dot]Hirdman[at]med[dot]lu[dot]se)

Qi Wang

PhD Student,qi [dot] wang [at] med [dot] lu [dot] se (qi[dot]wang[at]med[dot]lu[dot]se)

Runchuan Gu

PhD student, runchuan [dot] gu [at] med [dot] lu [dot] se (runchuan[dot]gu[at]med[dot]lu[dot]se)

Fanny Sveréus

PhD Student, fanny [dot] svereus [at] med [dot] lu [dot] se (fanny[dot]svereus[at]med[dot]lu[dot]se)

Ellen Broberg

Researcher, Ellen [dot] Broberg [at] med [dot] lu [dot] se (Ellen[dot]Broberg[at]med[dot]lu[dot]se)

Snejana Hyllen

Researcher, Snejana [dot] Hyllen [at] med [dot] lu [dot] se (Snejana[dot]Hyllen[at]med[dot]lu[dot]se)

Martin Stenlo

Researcher, Martin [dot] Stenlo [at] med [dot] lu [dot] se (Martin[dot]Stenlo[at]med[dot]lu[dot]se)

Martiné Wlosinska

Researcher, Martine [dot] Wlosinska [at] med [dot] lu [dot] se (Martine[dot]Wlosinska[at]med[dot]lu[dot]se)

Theodore Manolopoulos

Researcher

Haider Ghaiden

Researcher, Haider [dot] Ghaidan [at] med [dot] lu [dot] se (Haider[dot]Ghaidan[at]med[dot]lu[dot]se)

Annki Nilsson

Research assistant/nurse

Sujeethkumar Prithiviraj

Research assistant, sujeethkumar [dot] prithiviraj [at] med [dot] lu [dot] se (sujeethkumar[dot]prithiviraj[at]med[dot]lu[dot]se)

Eva-Marie Braf

Research assistant/nurse

Leif Pierre

Perfusionist, Leif [dot] Pierre [at] skane [dot] se (Leif[dot]Pierre[at]skane[dot]se)