One of the most exciting concepts in cancer research today is the cancer stem cell model where tumors are organized, as any other tissue, in a cellular hierarchy where the cancer stem cell sits at the apex, defined by its capacity to self-renew, the potential to differentiate into all cells of the tumor and the ability to proliferate and drive the expansion of the tumor. Besides, tumor expansion and metastasis is intimately linked to the generation of cells with stem cell features through the process of epithelial to mesenchynal transition (EMT). Understanding the mechanisms that regulate selfrenewal, mobilization and poliferation of cancer stem cells could lead to more effective treatments. Current efforts in drug discovery are directed towards interfering with the mechanisms that regulate self-renewal of stem cells, mainly the Wnt, Hh and Notch pathways, thus recently awarded patents and applications deal with these topics. There is however a strong need for marker identification and novel functional assays developed to test precisely those inhibitors in the stem cell population of tumors and so is reflected in that roughly one third of the patents targeted to breast cancer stem cells protect the use, identification and isolation of cancer stem cells. Finally, we discuss the recent observation that links the tumor suppressor p53 and induced pluripotency reprogramming which has lead to the speculation that cancer stem cells may arise through an altered reprogramming-like mechanism. Indeed some or all of the pluritpotency-associated genes are overexpressed in several forms of cancer, including breast cancer.
Neural repair and regeneration for tissue engineering is the most promising strategy for treating human brain neurological diseases. Main bottle neck of the clinical therapy is that no ideal scaffold biomaterials as vehicle of neural stem cells (NSCs) and growth factors have been developed yet, even for the clinical tests. To solve this problem, a lot of work has been done and numerous kinds of biomaterials have been studied. The interaction between NSCs and biomaterials, especially the regulation of NSCs by materials, plays an essential role during the scaffold biomaterial selection. The article gives an overview on the recent progresses on regulation of NSCs by biomaterial and shows some recent patents regarding the progress in the field.
Arthritic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA) cause considerable pain, reduced mobility and significant disability among affected patients and present a major challenge to clinicians and basic scientists due to the limited inherent repair capacity of articular cartilage. The poor capacity of articular cartilage for self-repair is largely due to its avascular nature and has resulted in the development of a variety of surgical treatments including Autologous Chondrocyte Implantation (ACI) or Autologous Chondrocyte Transplantation (ACT), microfracture and mosaicplasty. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with significant potential for chondrogenesis and new cartilage formation. Novel approaches using MSCs derived from bone marrow and adipose tissue have been proposed as alternatives to patient derived chondrocytes. In this paper we provide a scientific background to the biology of articular cartilage biology and its degeneration in arthritis. We also summarize some of the recent patents on applications of MSCs in articular cartilage tissue engineering and regenerative medicine for OA, RA and other joint diseases that involve cartilage degradation.
Recent progress and related patents in the field of bone marrow (BM)-resident adult stem/progenitor cell research have attracted well attention because these immature cells can act as the potential easily accessible cell sources for the cell transplantation in regenerative medicine and cancer therapies. The BM-resident hematopoietic stem/progenitor cells (HSCs and HPCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), endowed with a high self-renewal ability and multilineage differentiation potential, offer great promise to replace non-functional or lost cells and regenerate diseased and damaged tissues without a high-risk of graft rejection and major side effects. Particularly, the stimulation of the ex vivo or in vivo expansion and/or differentiation of a small subpopulation of BM-resident stem/progenitor cells or the use of genetically-modified BM stem/progenitor cells constitute potential cell-replacement and gene therapies with multiple applications in humans. Among the diseases that could be treated by the BM-derived stem/progenitor cell-based therapies, there are diverse hematopoietic, immune and vascular disorders, degenerative diseases such as Parkinsons and Alzheimers diseases, diabetes mellitus as well as skin, liver, lung, and heart disorders. In addition, a combination of the current cancer therapies with an adjuvant treatment consisting of an autologous or allogeneic BM-derived stem/progenitor cell transplantation also represents a promising strategy for treating and even curing diverse aggressive, metastatic, recurrent and lethal cancers.
Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer (HNPCC), represents 2% - 4% of all cases of colorectal cancer. LS is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to LS: mutS homolog 2 (MSH2); mutL homolog 1 (MLH1); mutS homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2); and postmeiotic segregation increased 1 (PMS1). The diagnostic features of LS have accumulated and been refined over time. Today, LS is defined by a set of clinical, pathological, and molecular features that encompass: a family history of colorectal cancer, a particular spectrum of extracolonic neoplasms, multiple colorectal tumors, early onset of cancer, particular histological features among colorectal cancers, presence of DNA microsatellite instability, loss of expression of DNA mismatch repair proteins, and germline mutation in a DNA mismatch repair gene. This review provides an overview of the diagnosis and management of LS patients, including some recently reported patents.
Dendritic cells (DCs) play a crucial role in maintaining the immune system. DC-based immunotherapy is known as the “cancer vaccine” for advanced cancers and to prevent recurrence. Though DC-based cancer immunotherapy has been suggested as a potential treatment for various kinds of malignancies, its clinical efficacies in many human trials are still insufficient. To identify the causes of these low efficacies, many investigators have focused on the numbers of administered DCs, how they are activated, which type is best, and so on. This review focuses primarily on patents analysis of recently developed DC-based cancer immunotherapies. We also analyze the critical factors of DC-based cancer immunotherapy to best optimize the development of these novel technologies.
This article reviews the scientific and intellectual property development of a biotechnology platform in regenerative medicine called Human Myoblast Genome Therapy (HMGT), known previously as Myoblast Transfer Therapy (MTT). Myoblasts are the least differentiated myogenic cells capable of extensive division, natural cell fusion, nucleus transfer, cell therapy and genome therapy. Myoblasts cultured from muscle biopsy survive, develop and function, after transplantation in animal studies and clinical trials, to revitalize degenerative organs in heart failure, ischemic cardiomyopathy, Type II diabetes, muscular dystrophies, aging dysfunction and disfigurement. Myoblasts have also been used to enhance skin and muscle appearance in cosmetology. HMGT replenishes live cells and genetically repairs degenerating myofibers. It is the worlds first human gene therapy when it replenished dystrophin in Duchenne muscular dystrophy as reported in Lancet on July 14, 1990. Data from FDA- approved Phase II/III muscular dystrophy clinical trials demonstrated significant safety and efficacy to merit allowance of cost recovery in consecutive years. Data from FDA- and EMA- approved Phase II/III ischemic cardiomyopathy clinical trials demonstrated significant safety and efficacy. This review also provides in-depth analyses of key factors related to success and failure of HMGT procedures. Future development will focus on myoblasts transduced with VEGF165 using nanoparticles or liposomes that are promising biologics for angiomyogenesis. Automated cell processors, myogenic cell injection catheters and methods of use have been patented to complement the HMGT technology.
It has been challenging to develop methods that induce the repair and regeneration of cartilage because of the unique characteristics of this tissue. Cartilage lacks blood vessels and lymphatic nerve systems. Moreover, chondrocytes are fed by diffusion via the perichondrium, which is helped by the pumping action generated by compression of the articular cartilage or flexion of the elastic cartilage. Thus, compared to other tissues, the growth and repair of cartilage are slow. Moreover, it is now widely understood that the physiological development and maintenance of chondrocytes, particularly those in articular cartilage, are dictated by mechanical forces. Consequently, to generate cartilage-like constructs in vitro and cartilage repair in vivo for tissue engineering and regenerative medicine purposes, these cartilagespecific characteristics, including the dependence of chondrocytes on mechanical forces, have to be considered. In recent times, the ability of stem cells to promote tissue regeneration has been the subject of great interest. Thus, in this review, we focus on stem cell-based methods of inducing cartilage regeneration and repair, and show that a deeper understanding of chondrocyte biology and mechanophysiology may lead to novel patents in this field in the future.
Since the first report on induced pluripotent stem (iPS) cells in 2006, iPS cells have attracted great public attention and research interest. Like embryonic stem (ES) cells, iPS cells are capable to self-renew infinitely, and maintain the developmental potential to differentiate into any types of cells in the body. More importantly, derivation of iPS cells is independent of embryos, circumventing the ethic issue tightly bound with ES cells. Thus, iPS cells seem to be a promising cell source for regenerative medicine. In this review, we summarize the recent patents and progress in derivation of iPS cells.