“Recent studies have revealed that adult stem cells such as bone marrow derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells may be a potent next generation therapy for COPD”.
This is the statements that Dr Bruno D’Agostino and other scientist of the Naples University (Italy), published on October 2010 in Expert Opinion on Biological Therapy Magazine, an international journal publishing that review articles and original papers on all aspects of biological therapy, providing expert opinion around those fields.
At this review you can find a summary of this interesting paper. (Expert Opin. Biol. Ther. (2010) 10(5).
Bone marrow contains hematopoietic stem cells (HSCs), which characteristically differentiate into every type of mature blood cell, and mesenchymal stem cells (MSCs), which differentiate into fat, bone, cartilage and other mesenchymal tissues. Many studies have shown that cells derived from adult bone marrow are able to produce a variety of non-hematopoietic cells both in vitro and in vivo making them one of the best candidate for lung repair. Of the tissues with reported stem or progenitor activity, the one used extensively in cell-based therapies is bone marrow.
In humans, lung specimens from some clinical bone marrow transplant recipients demonstrate pulmonary chimerism (more than one set of DNA or two different cells) for both epithelial and endothelial cells. These findings were also repeated in male recipients of a female lung allograft, where it was also shown that cell engraftment occurred in the severely injured area.
This latter observation is consistent with another report in which the engraftment of the stem cells was greater when the parenchyma was injured before transplantation (e.g., by radiation injury). These studies support the notion that preexisting injury increases mobilization and recruitment of bone-marrow-derived cells within the inflammatory area. Therefore, the hypothesis that inflammatory stimuli can increase release of soluble factors by airway epithelium capable of playing an important role in cells recruitment from bone marrow to the lung was supported.
Recently, among bone-marrow-derived cells, MSCs are emerging as a therapeutic modality in various inflammatory diseases for their anti-inflammatory and immunomodulatory properties. The first evidences of the potential anti-inflammatory role of MSCs in lung diseases have been published at the beginning of the last decade.
The Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (GOLD) defines COPD as a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients.
This disease is a common cause of morbidity and mortality worldwide representing the fifth leading cause of death in the developed countries. Further increases in its prevalence and mortality are expected in the coming decades.
Cigarette smoking has been shown to be the most important risk factor and accounts for 80 ± 90% of the risk of developing COPD. In fact, the inhalation of noxious particles, such as cigarette smoke, causes the influx of inflammatory cells, in particular neutrophils, macrophages and CD8+ T lymphocytes, into the airways and lungs, leading to chronic inflammation.
According to the most recent clinical guidelines for COPD, the available treatments, both pharmacological and nonpharmacological, are essentially symptomatic, with the exception of two interventions that may also increase life expectancy: smoking cessation in patients with COPD, and long-term oxygen treatment in patients with COPD and respiratory failure. Bronchodilator therapy is a key component of treatment for patients with COPD at different stages of severity.
MSCs are considered as a therapy in COPD more for their immunomodulatory effects than for the ability to regenerate type I and II cells in the airspace.
MSCs are non-hematopoietic stem cells of mesodermal origin showing a multi-lineage potential, as they have the capacity to give rise to skeletal muscle cells, blood, fat, vascular and urogenital systems, and to connective tissues throughout the body. Due to their unlimited self-renewal capacity, MSCs show a high expansion potential. In addition, these cells show genetic and phenotypic stability, can be easily isolated from a small aspirate of bone marrow, expanded with high efficiency, shipped from the laboratory to the bedside and are compatible with different delivery methods and formulations.
MSCs are able to migrate to sites of tissue injury and have strong immunosuppressive properties that can be exploited for successful autologous as well as heterologous transplantations. Moreover, they are able to protect lung tissue by suppression of pro-inflammatory cytokines.
Stem-cell-based therapies may represent new therapeutic approaches for COPD that currently lacks efficient treatment. Because the rate of engraftment and differentiation is generally low following MSC therapy for lung injury, the positive therapeutic effects mediated by MSCs are probably mainly due to their ability to produce paracrine factors and to modulate the inflammatory response. In this way, MSCs could serve as cellular factories that secrete mediators to stimulate the repair of tissues, by acting on endogenous lung stem cells, or elicit other beneficial effects on the surrounding host tissue. In such cases, the overall effect may be the combined enhancement of stem cell survival as well as an enhancement of the local tissue environment.
The above mentioned studies provide direct evidence that MSCs can potentially be used for COPD, or other lung disease, but the precise mechanism underlying this process needs to be understood to best achieve this goal. Human MSCs are obtained directly from patient, thus the subsequent use of these cells in the clinical setting would have the advantage that since MSCs are autologous, they would not be rejected after cell transplantation. Despite their low capability to home into the lung and differentiate into lung cells, they can have beneficial effects.
Importantly, several observations provide evidence that MSCs can act through a combination of paracrine effects that could stimulate the expansion, homing and differentiation of endogenous stem cells on one hand and the differentiation of MSCs toward alveolar epithelial cells, endothelial cells, fibroblasts and bronchial epithelial cells on the other.