**6. Perspectives and challenges**

468 Chronic Obstructive Pulmonary Disease – Current Concepts and Practice

in CVF; in spite of this fact, an important aspect is that the functional parameters remained

An interesting information turned out in the long term results, approximately 2 years of clinical monitoring. The spirometry parameters along the post transplantation period, by and large, maintain a certain regularity and similarity to those found before the procedure. One of the research subject disclosed a significant increase in the forced vital capacity, after 1 year and 3 months of treatment (Figure 8); The analysis of this parameter suggests a

Fig. 8. Percentage of predicted and absolute values from a patient spirometry until 1 year

The results from this clinical protocol show the procedure should be conducted at an earlier stage, that is, at a less advanced stage of the pathology. As mentioned, the laboratorial analysis, confirmed by clinical response, has reported a significant improvement in all patients, chiefly in the first 30 days after the procedure was carried out. After this period, laboratory tests displayed a tendency to decrease; however they did not drop to the base values obtained before the BMMC therapy treatment. These results advance the possibility that cell therapy may be applied in repeated doses from time to time for the purpose of

Another protocol under registration with Clinical Trials (NTC00683722) corresponds to a multicenter, double-blind, placebo controlled phase II study for patients with moderate to severe COPD. The clinical protocol, sponsored by Osiris Therapeutics Inc. (Columbia, MD), concerns the employment of *ex vivo* cultured adult human SC (PROCHYMAL) in the treatment of pulmonary emphysema. The purpose comprehends the evaluation of safety

and 3 months after BMMC autologous transplant.

stimulating pulmonary regeneration.

and efficacy of MSC multiple infusion.

always higher than the ones found before the procedure.

proximity to normality and reduction of the severity of the disease.

COPD represents a serious public health problem, which, according to the latest projections of the World Health Organization, should gradually change for the worse in the coming years, with a great impact on the economy, on a global scale.

The incorporation of new drugs having more effectiveness and longer effect unquestionably has contributed to the improvement in quality of life of the patients; however, up to now, no significant change in the natural history of the disease has been achieved. In this context, cell therapy turns out as a potentially promising treatment option, which, perhaps, may represent a change of paradigm in therapeutics and in the natural course of the disease.

The results achieved at our laboratory and by several other coworkers, at different research centers, have shown a morphological recovery of the pulmonary parenchyma in animals with experimentally-induced emphysema by the employment of proteases and/or cigarette smoke. From said results, a pioneer treatment with BMMC pool was administered for patients with emphysema in advanced stage. It is a project in an initial phase and the sample of treated patients is still small, which limit the analyses from the statistical point of view. At our research center, a new project will soon start. It will comprehend a larger sample (about 40 patients) and the employment of a new methodology, which the use of MSC.

Notwithstanding the statistical limitations, the pioneer publication of the results by our research group (Ribeiro-Paes *et al*., 2011), has afforded the preparation of some logical inferences and methodological suggestions which will be incorporated into future projects. The use of MSC obtained from adipose tissue has disclosed a highly promising future perspective. Furthermore, the feasibility of establishing a protocol with repeated SC infusions should also be taken into account, just like in chronic treatments with drugs.

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