Authors: Stergios Moschos, Maja Mandic, John Kirkwood, Walter Storkus, and Michael Lotze
Title: Current and Future Considerations in the Use of Mechanical Circulatory Support Devices
Summary: Heart failure (HF) is a major public health problem in the United States, and its prevalence is likely to increase with the aging U.S. population. Mechanical circulatory support (MCS) utilizing bladder-based blood pumps generating pulsatile flow has been reserved for patients with severe HF failing medical therapy. As MCS technology has advanced to include rotary blood pumps, so has our understanding of the biological and clinical responses to MCS, which in turn has altered the risk/benefit profile of this therapy. This may lead to paradigm shifts in device usage from support of end-stage HF to temporary support for recovery of cardiac function and earlier usage, to, ultimately, prevention of disease progression. This review serves to explore the current state and future opportunities of MCS within our larger understanding of the epidemiology, pathophysiology, and treatment options for HF.
Authors: Mihaela Crisan, Solomon Yap, Louis Casteilla, Chien-Wen Chen, Mirko
Corselli, Tea Soon Park, Gabriella Andriolo, Bin Sun, Bo Zheng, Li Zhang,
Cyrille Norotte, Pang-Ning Teng, Jeremy Traas, Rebecca Schugar, Bridget M. Deasy, Stephen Badylak, Hans-Jörg Bűhring, Jean-Paul Giacobino, Lorenza Lazzari, Johnny Huard and Bruno Péault
Title: A Perivascular Origin for Mesenchymal Stem Cells in Multiple Human Organs
Summary: Mesenchymal stem cells (MSC), the archetypal multipotent progenitor cells derived in cultures of developed organs, are of unknown identity and native distribution. We have prospectively identified perivascular cells, principally pericytes, in multiple human organs including skeletal muscle, pancreas, adipose tissue and placenta, on CD146, NG2 and PDGF-Rβ expression and absence of hematopoietic, endothelial and myogenic cell markers. Perivascular cells purified from skeletal muscle or nonmuscle tissues were myogenic in culture and in vivo. Irrespective of their tissue origin, long-term cultured perivascular cells retained myogenicity, exhibited, at the clonal level, osteogenic, chondrogenic and adipogenic potentials, expressed mesenchymal stem cell markers and migrated in a culture model of chemotaxis. Expression of MSC markers was also detected at the surface of native, non-cultured perivascular cells. Thus, blood vessel walls harbor a reserve of progenitor cells that may be integral to the origin of the elusive MSC and other related adult stem cells.
Authors: Odoux C, Fohrer H, Hoppo T, Guzik L, Stolz DB, Lewis DW, Gollin SM, Gamblin TC, Geller DA, Lagasse E.
Title: A stochastic model for cancer stem cell origin in metastatic colon cancer.
Summary: Human cancers have been found to include transformed stem cells that may drive cancer progression to metastasis. Here, we report that metastatic colon cancer contains clonally derived tumor cells with all of the critical properties expected of stem cells, including self-renewal and the ability to differentiate into mature colon cells. Additionally, when injected into mice, these cells initiated tumors that closely resemble human cancer. Karyotype analyses of parental and clonally derived tumor cells expressed many consistent (clonal) along with unique chromosomal aberrations, suggesting the presence of chromosomal instability in the cancer stem cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stem cells and the stochastic model, driven by the observation of chromosomal instability.
Authors: Velliste, M, Perel S, Spalding MC, Whitford AS, Schwartz AB
Title: Cortical control of a prosthetic arm for self-feeding
Summary: Arm movement is well represented in populations of neurons recorded from the motor cortex. Cortical activity patterns have been used in the new field of brain-machine interfaces to show how cursors on computer displays can be moved in two- and three-dimensional space. Although the ability to move a cursor can be useful in its own right, this technology could be applied to restore arm and hand function for amputees and paralysed persons. However, the use of cortical signals to control a multi-jointed prosthetic device for direct real-time interaction with the physical environment (’embodiment’) has not been demonstrated. Here we describe a system that permits embodied prosthetic control; we show how monkeys (Macaca mulatta) use their motor cortical activity to control a mechanized arm replica in a self-feeding task. In addition to the three dimensions of movement, the subjects’ cortical signals also proportionally controlled a gripper on the end of the arm. Owing to the physical interaction between the monkey, the robotic arm and objects in the workspace, this new task presented a higher level of difficulty than previous virtual (cursor-control) experiments. Apart from an example of simple one-dimensional control, previous experiments have lacked physical interaction even in cases where a robotic arm or hand was included in the control loop, because the subjects did not use it to interact with physical objects-an interaction that cannot be fully simulated. This demonstration of multi-degree-of-freedom embodied prosthetic control paves the way towards the development of dexterous prosthetic devices that could ultimately achieve arm and hand function at a near-natural level.
Title: Regional anatomic and age effects on cell function of human adipose-derived stem cells.
Summary: Adipose tissue has been shown to contain adult mesenchymal stem cells that have therapeutic applications in regenerative medicine. There is evidence that the ability of adipose precursor cells to grow and differentiate varies among fat depots and changes with age. Defining these variations in cell function and molecular mechanisms of adipogenesis will facilitate the development of cell-based therapies. We compared cells harvested from 5 different subcutaneous (SC) adipose depots in 12 female patients classified into 3 age ranges (25-30, 40-45, and 55-60 years old). Capacity for differentiation of isolated adipose-derived stem cells (ASCs) with and without ciglitazone, a strong peroxisome proliferator activated receptors (PPAR)-gamma agonist, was assessed in vitro. ASCs were also characterized by lipolytic function, proliferation, and sensitivity to apoptosis. Additionally, PPAR-gamma-2 protein expression was determined. We observed a difference in the apoptotic susceptibility of ASCs from various SC depots, with the superficial abdominal depot (above Scarpas layer) significantly more resistant to apoptosis when compared with the 4 other depots. We have also demonstrated that a PPAR-gamma agonist aids in the induction of differentiation in cells from all depots and ages. Although sensitivity to apoptosis was linked to anatomic depot, differences in cell proliferation were related primarily to age. Stimulated free glycerol release has been shown to be highest in the arm depot. The arm depot has also consistently shown expression of PPAR-gamma-2 with and without a PPAR-gamma agonist. Younger patients have increased PPAR-gamma-2 expression in all depots, whereas the older patients have consistent elevated expression only in the arm and thigh depots. We have shown there is variability in function of ASCs that have been harvested from different SC depots. Additionally, we have shown age-related changes in function. These data will help select patients and cell harvest sites most suitable for tissue engineering therapies.
Authors: Yoram Vodovotz, Marie Csete, John Bartels, Steven Chang, Gary An
Title: Translational Systems Biology of Inflammation
Summary: Inflammation is a complex, multi-scale biologic response to stress that is also required for repair and regeneration after injury. Despite the repository of detailed data about the cellular and molecular processes involved in inflammation, including some understanding of its pathophysiology, little progress has been made in treating the severe inflammatory syndrome of sepsis. To address the gap between basic science knowledge and therapy for sepsis, a community of biologists and physicians is using systems biology approaches in hopes of yielding basic insights into the biology of inflammation.
‘‘Systems biology’’ is a discipline that combines experimental discovery with mathematical modeling to aid in the understanding of the dynamic global organization and function of a biologic system (cell to organ to organism). We propose the term translational systems biology for the application of similar tools and engineering principles to biologic systems with the primary goal of optimizing clinical practice. We describe the efforts to use translational systems biology to develop an integrated framework to gain insight into the problem of acute inflammation. Progress in understanding inflammation using translational systems biology tools highlights the promise of this multidisciplinary field. Future advances in understanding complex medical problems are highly dependent on methodological advances and integration of the computational systems biology community with biologists and clinicians.
Authors: Bo Zheng, Baohong Cao, Mihaela Crisan, Bin Sun, Guangheng Li, Alison Logar, Solomon Yap, Jonathan B Pollett, Lauren Drowley, Theresa Cassino, Burhan Gharaibeh, Bridget M Deasy, Johnny Huard & Bruno Péault
Title: Prospective Identification of Myogenic Endothelial Cells in Human Skeletal Muscle
Summary: This manuscript documents anatomic, molecular and developmental relationships between endothelial and myogenic cells within human skeletal muscle. Cells coexpressing myogenic and endothelial cell markers (CD56, CD34, CD144) were identified by immunohistochemistry and flow cytometry. These myoendothelial cells regenerate myofibers in the injured skeletal muscle of severe combined immunodeficiency mice more effectively than CD56+ myogenic progenitors. They proliferate long term, retain a normal karyotype, are not tumorigenic and survive better under oxidative stress than CD56+ myogenic cells. Clonally derived myoendothelial cells differentiate into myogenic, osteogenic and chondrogenic cells in culture. Myoendothelial cells are amenable to biotechnological handling, including purification by flow cytometry and long-term expansion in vitro, and may have potential for the treatment of human muscle disease.