Daar and Greenwood (2007) stated that “regenerative medicine aims at repair, replacement of cells or organs to recover the impaired function’ (1). It helps the body to form new functional tissue. It includes cell therapies, tissue engineering, gene therapy and biomedical engineering techniques” (2).

So, cell therapy and tissue engineering are parts of the field of regenerative medicine, whose aim is production of safe and effective therapies. Stem cells present in almost every type of tissues and represent an endogenous system of regeneration and repair. Therefore, stem cells represent great hope for the future of translational medicine (3).

The epithelium of the whole respiratory system developed from a region of anterior ventral foregut endoderm, marked by the transcription factor Nkx2-1. After lung maturation, the epithelium differs along the proximaldistal axis, both in cellular structure and structural organization and, related to this, in stem cell composition and strategies for repair (4).

Different regions of the lung contain different populations of epithelial cells that function as adult stem cells, as defined by their ability to self-renewal and differentiation during lung injury (4).

One approach is the interactions between epithelial and mesenchymal cells in the reparative niche because crosstalk between these populations is known to be an essential process for proper development of the lung. Other signaling pathways, such as Wnt and Notch, known to play important roles in stem cell self-renewal and differentiation also play key roles in lung repair and regeneration. Wnt signaling is an essential regulator of early lung endoderm specification and development and has been implicated in regulating regenerative responses. Using Wnt reporter lines, several groups have demonstrated activation of canonical Wnt signaling in various compartments in the lung undergoing active regrowth and regeneration. In the airway epithelium, Wnt signaling is activated upon secretory cell depletion by naphthalene treatment. Activation of Wnt signaling through loss of the critical transcription factor Gata6 leads to expansion of the putative BASC population after naphthalene injury (9).

In humans, stem cells can be subdivided into two main categories: intrinsic and extrinsic stem cells (10). A large variety of cell types has been used for regenerative medicine, including adult cells, resident tissue specific stem cells, bone marrow stem cells, Umbilical cord blood stem cells, embryonic stem cells and the recent breakthrough discovery of induced pluripotent stem cells from mature/adult cells (iPS) (called reprogramming, induced a pluripotent state in a previously differentiated cell type) (11).

Many studies have provided strong evidence that stem cells (and mainly mesenchymal stem cells, MSC) can mediate tissue repair through the modulation of the local environment, affecting the immune/inflammatory response, sustaining angiogenesis and establishing co-operative effects with the resident cells, overall resulting in a significant cytoprotective and pro-survival beneficial influence. The mechanism through which this regenerative result is achieved seems to depend more on the secretion of specific bioactive factors, rather than the direct differentiation of the transplanted stem cells in the host tissue, given the low incidence and poor efficiency of their survival and therapeutically relevant level of engraftment. This hypothesis is defined as paracrine effect and the composite set of the cytokines, chemokines and growth factors regulate many biological activities and secreted from stem cells (or shed from their membranes) is defined as secretome (17).

Some reports have demonstrated that the administration of stem cell-conditioned medium, which contains all the bioactive factors released by the cells in culture, can exert the same regenerative effect obtained with cell transplantation (17).

Microvesicles have been described as key regulators of the stem cell paracrine activity. The term of extracellular microvesicles (MVs) was first introduced to indicate nano-sized bodies released as shedding vesicles by various cell types into the extracellular environment (17).

Stem cells have many clinical implications in the lung. Treatment by cell therapy could be envisaged for acute disorders such as ARDS, or more chronic disorders such as emphysema and lung fibrosis. Nevertheless, the consensus is now that respiratory epithelial engraftment is a very rare event, and as such cellular repair is not thought to be realistic at present. Engraftment of stem cells can also be used for genetic therapy. In a mouse model, bone marrow stem cells were genetically altered with a viral vector to express GFP. These transplanted cells then engrafted in the recipient lung, differentiating into lung epithelium while maintaining long-term transgene expression. Stem cells may therefore act as genetic vectors in certain diseases needing replacement of a protein or DNA. Within respiratory medicine, cystic fibrosis (CF) is a devastating illness that may similarly benefit from such an approach. As well as cellular and genetic therapy for lung diseases, an appreciation of stem cells may improve the understanding and treatment of certain malignancies. There is an increasing belief that cancers contain a small number of cancer stem cells and that the majority of cells within the tumor are not capable of tumor initiation. Furthermore, these cancer stem cells are often relatively quiescent, suggesting that conventional anti proliferative chemotherapy agents may spare these cells, leading to tumor recurrence. A greater understanding of the role of cancer stem cells may help to develop specific therapies targeting them and not the rapidly proliferating daughter cells. In this instance, the detection of cancer stem cells pecific surface markers or unique molecular targets would allow directed molecular therapy (23).