Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies

BACKGROUND: Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality. METHODS: In this study we demonstrate that therapeutic lung cells, termed "lung spheroid cells" (LSCs) can be generated from minimally invasive transbronchial lung biopsies using a three-dimensional culture technique. The cells were then characterized by flow cytometry and immunohistochemistry. Angiogenic potential was tested by in-vitro HUVEC tube formation assay. In-vivo bio- distribution of LSCs was examined in athymic nude mice after intravenous delivery. RESULTS: From one lung biopsy, we are able to derive >50 million LSC cells at Passage 2. These cells were characterized by flow cytometry and immunohistochemistry and were shown to represent a mixture of lung stem cells and supporting cells. When introduced systemically into nude mice, LSCs were retained primarily in the lungs for up to 21 days. CONCLUSION: Here, for the first time, we demonstrated that direct culture and expansion of human lung progenitor cells from pulmonary tissues, acquired through a minimally invasive biopsy, is possible and straightforward with a three-dimensional culture technique. These cells could be utilized in long-term expansion of lung progenitor cells and as part of the development of cell-based therapies for the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF)

Auditing; Petunjuk Praktis Pemeriksaan oleh Akuntan Publik, Buku 1

1 jil., 468 hlm., 19 x 26 cm

The Trilemma in History:Tradeoffs among Exchange Rates, Monetary Policies,and Capital Mobility

Recently, the political economy of macroeconomic policy choice has increasingly been guided by the simple prescriptions of the classic trilemma. For example, policymakers often speak of the hollowing out of exchange rate regimes in a world of unstoppable capital mobility; and policy autonomy and a fixed nominal anchor present an unpleasant dichotomy for emerging markets beset by the fear of floating. Yet the trilemma is not an uncontroversial maxim, and its empirical foundations deserve greater attention. Some authors (e.g., Calvo and Reinhart 2001, 2002) have argued that under the modern float there could be limited policy autonomy given the rapid international transmission of interest rate shocks; others (e.g., Bordo and Flandreau 2003) that even under the classical gold standard there actually was considerable policy autonomy given the gold point spread and the use of gold devices and other tricks. Such arguments turn the trilemma on its head. Resolving this debate is ultimately an empirical matter, where the broadest span of data should be scrutinized. Using new techniques to study the coherence of international interest rates at high frequency, in conjunction with an examination of capital mobility policies and a data-based classification of exchange rate regimes, we look at the empirical content of the trilemma based on consistent data over 130+ years. On the whole, the predictions of this influential adage are borne out by history.