Adipose Tissue Transfer, Lung Scaffolds: The Future of Stem Cells in COPD

Emerging evidence from preclinical and clinical trials has demonstrated the potential of stem cells to repair lung tissue in chronic obstructive pulmonary disease (COPD).¹

Stem Cell Therapy May Provide Unmet Needs

Clinicians are clamoring for new therapies to address the damage to airways and lung parenchyma because no current therapy can completely reverse damage from COPD, which is projected to become the world’s third most fatal disease by 2020.²

A mismatch between demand and supply of stem cells exists due to the ethical considerations involved in procuring them. The main sources are embryonic blastocysts, fetuses, umbilical cord blood; adult blood, bone marrow, adipose tissue, muscle, teeth; and the placenta following birth. Because adult-derived stem cells can renew themselves and transform into other types of cells, much of the research has been focused in this area.²

Stem cells have the natural ability to transform into specialized cells and in infinite numbers. Mesenchymal stem cells (MSC), which are taken from the bone marrow of adults, provide homeostasis and can travel to repair injured tissue. MSCs can also be harvested from damaged tissues in contact with vascular and connective tissues, blood, and skeletal muscle. MSCs are particularly valuable clinically because their molecular structure limits immune system recognition.²

“The difficulties of pharmacological treatment in some phenotypes of the disease are not able to give an adequate therapeutic response to patients, so we must push the researchers to new frontiers,” said pulmonologist Domenico M. Toraldo MD, from the Department of Rehabilitation, Respiratory Care Unit of the Azienda Sanitaria Locale in Lecce, Italy, in an interview with Pulmonology Advisor. “The bronchodilator drugs and topical steroids are symptomatic and slow the evolution of lung disease.”

Adipose Stem Cell Delivery in COPD

In the case of autologous adipose tissue transfers, many procedures harvest cells from the bone marrow via puncture of the iliac crest, which can increase the risk for infection and considerable pain. In addition, subcutaneous adipose tissue yields 500 times the amount of cells that bone marrow does. Thus far, most of the procedures in human trials have involved autologous transfers of adipose stem/stromal cells (ASC).¹

In murine studies, ASC reduced neutrophil infiltration and airway inflammation and normalized the right ventricle area. Although these benefits were seen in mice with COPD, ASC demonstrated a reduction in structural changes in the lung caused by emphysema. One of the most promising areas of investigation is the use of ASC to improve mean linear intercept (MLI) or mean distances in lung airspaces.¹

ASC delivery to the lungs is one of many preclinical investigations currently underway. Kim and colleagues tested ASC delivery via artificial nanovesicles injected into mice with emphysema.³ Nanovesicles could enable clinicians to deliver smaller ASC amounts more rapidly in a 100 nm-sized sphere than those possible with natural exosomes injected into the lung. The mice injected with nanovesicles produced more fibroblast growth factor 2, a compound essential for lung development, than mice injected with natural ASC exosomes.³

Lung Scaffolds Enable Tissue Engineering

Even after patients in end-stage disease receive lung transplantation, the survival rate is only 50% after 5 years, which has not improved in decades. Studies of lung scaffolds may offer alternatives to patients awaiting transplant by providing transplantable ex vivo lung tissue and thus avoid the rejection of allograft lungs.⁴