干细胞治疗与牙周组织再生

干细胞是具有自我复制和多向分化潜能的原始细胞,在一定条件下可以分化成多种功能细胞或组织器官,故又称其为"万用细胞",干细胞治疗就是利用其多向分化的特点,以达到修复病变细胞或重建功能正常的细胞和组织的目的。牙周组织再生一直是牙周病治疗中要攻克的难题,干细胞治疗的研究为牙周组织再生提供了新的思路和方法。本文就可用于牙周再生的干细胞和相关治疗技术作一综述。

2014自然杂志中国论坛:以基因组学和干细胞为基础的治疗:打造未来个性化医疗会议通知(第一轮)

2014年自然杂志中国论坛“以基因组学和干细胞为基础的治疗：打造未来个性化医疗”定于2014年5月29日-31日，在中国广州花园酒店举行。

Inflammatory bowel disease: Moving toward a stem cell-based therapy

The incidence and prevalence of Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel diseases (IBD), are rising in western countries. The modern hygienic lifestyle is probably at the root of a disease where, in genetically susceptible hosts, the intestinal commensal flora triggers dysregulated immune and inflammatory responses. Current therapies ranging from anti-inflammatory drugs to immunosuppressive regimens, remain inadequate. Advances in our understanding of the cell populations involved in the pathogenetic processes and recent findings on the regenerative, trophic and immunoregulatory potential of stem cells open new paths in IBD therapy. Hematopoietic and mesenchymal stem cells are catalyzing the attention of IBD investigators. This review highlights the pivotal fi ndings for stem cell-based approaches to IBD therapy and collects the encouraging results coming in from clinical trials.

Stem cells for end stage liver disease: How far have we got?

End stage liver disease (ESLD) is a health problem worldwide. Liver transplantation is currently the only effective therapy, but its many drawbacks include a shortage of donors, operative damage, risk of rejection and in some cases recidivism of the pre-transplant disease. These factors account for the recent growing interest in regenerative medicine. Experiments have sought to identify an optimal source of stem cells, sufficient to generate large amounts of hepatocytes to be used in bioartificial livers or injected in vivo to repair the diseased organ. This update aims to give non-stem cell specialists an overview of the results obtained to date in this fascinating field of biomedical research.

Adult stem cells as a tool for kidney regeneration

Kidney regeneration is a challenging but promisingstrategy aimed at reducing the progression to end-stagerenal disease （ESRD） and improving the quality of life of patients with ESRD. Adult stem cells are multipotent stem cells that reside in various tissues, such as bone marrow and adipose tissue. Although intensive studies to isolate kidney stem/progenitor cells from the adult kidney have been performed, it remains controversial whether stem/progenitor cells actually exist in the mammalian adult kidney. The effcacy of mesenchymal stem cells （MSCs） in the recovery of kidney function has been demonstrated in animal nephropathy models, such as acute tubular injury, glomerulonephritis, renal artery stenosis, and remnant kidney. However, their benefcial effects seem to be mediated largely via their paracrine effects rather than their direct differentiation into renal parenchymal cells. MSCs not only secrete bioactive molecules directly into the circulation, but they also release various molecules, such as proteins, mRNA, and microRNA, in membrane-covered vesicles. A detailed analysis of these molecules and an exploration of the optimal combination of these molecules will enable the treatment of patients with kidney disease without using stem cells. Another option for the treatment of patients with kidney disease using adult somatic cells is a direct/indirect reprogramming of adult somatic cells into kidney stem/progenitor cells. Although many hurdles still need to be overcome, this strategy will enable bona fde kidney regeneration rather than kidney repair using remnant renal parenchymal cells.

Different modes of renal proximal tubule regeneration in health and disease

Tissues are equipped with reasonable strategies for re-pair and regeneration and the renal proximal tubule （PT）is no exception. New information has become availableon the mode of PT regeneration in mammals. Unlikethe intestinal epithelium with a high rate of turnovermaintained by the stem cell system, the kidney has lowturnover under normal physiological conditions. The PTseems to be maintained physiologically by hyperplasia,a regenerating system with self-renewal of mature tu-bular cells. This mode of regeneration is advantageousfor effective replenishment of randomly isolated andeliminated tubular cells by self-renewal of adjacentcells. On the other hand, it has been suggested thatdedifferentiation of mature tubular cells plays a role inregeneration after acute kidney injury. Recent studiesemploying genetic labeling and DNA-labeling tech-niques have confrmed that the proliferation of preex-isting injured mature tubular cells contributes mainlyto PT regeneration in ischemic reperfusion injury. Thismode of regeneration is beneficial with regard to therapid reparation of focally injured tubules often inducedby ischemic reperfusion injury. What happens, howeverwhen the PT is homogeneously injured with almost noremaining surviving cells？ Is the PT equipped with another backup regeneration system, e.g., the stem cell system？ Is it possible that certain types of renal injuries evoke a stem cell response whereas others do not？ This review focuses on all three possible modes of tis-sue regeneration （compensatory hyperplasia, dediffer-entiation and stem cell system） in mammals and their involvement in PT regeneration in health and disease.

Implications of Stem Cells and Cancer Stem Cells for Understanding Fomation and Therapy of Cancer

Most cancers are heterogeneous with respect to proliferation and differentiation. There is increasing evidence suggesting that only a minority of cancer cells, tumorigenic or tumor initiating cells, possess the capacity to proliferate extensively and form new hematopoietic cancer or solid tumors. Tumor initiating cells share characteristics required for normal stem cells. The dysregulation of self-renewal and proliferation of stem cells is a likely requirement for cancer development. This review formulates a model for the origin of cancer stem cells and regulating self-renewal which influences the way we study and treat cancer.

Improving cancer therapy by targeting cancer stem cells:Directions, challenges, and clinical results

Cancer stem cells （CSC） are a rare cell population withina tumor characterized by the ability to form tumorsfollowing injection into an immunocompromised host.While the role of CSC has been clearly established inanimal models, evidence of their clinical relevance hasbeen harder to demonstrate. A number of markers,or combination thereof, have been used to detect andmeasure, although non-specifically, CSC in almost allhuman tumors. Several pathways have been identifiedas crucial for, but not necessarily unique to, CSC surviva and proliferation, and novel agents have been designed to target such pathways. A number of such agents have entered early phase development. Further, drugs that have long been marketed for non-oncological indications have been redirected to oncology as they appear to affect one or more of such pathways. This article aims to review the available evidence on the clinical relevance of CSC from a drug development standpoint and the results of early phase clinical trials of agents interfering with the above pathways. It also discusses limitations of current clinical trial design and endpoints to demonstrate anti-CSC activity as well as possible strategies to overcome these limitations.

Intravenously Injected Mesenchymal Stem Cells Home to Infarcted Myocardium Without Altering Cardiac Function

Background:Systemic delivery of mesenchymal stem cells (MSCs) to the infarcted myocardium is an attractive noninvasive strategy, but therapeutic effect of this strategy remain highly controversial. Methods: Myocardial infarction was induced in female Sprague-Dawley rats by transient ligation of the left anterior descending coronary artery for 60 min. Either 2.5×106 DiI-labeled MSCs or equivalent saline was injected into the tail vein at 24 h after infarction.Results: Three days later, MSCs localized predominantly in the infarct region of heart rather than in the remote region. MSCs were also observed in spleen, lung and liver. At 4 weeks after infarction, echocardiographic parameters, including ejection fraction, fractional shortening, left ventricular end-diastolic and end-systolic diameters, were not significantly different between MSCs and saline groups. Hemodynamic examination showed that ±dp/dtmax were similar between MSCs and saline-treated animals. Histological evaluation revealed that infarct size and vessel density were not significantly changed by MSCs infusion.Conclusion: Intravenously injected MSCs can home to infarcted myocardium, but plays a limited role in cardiac repair following myocardial infarction.

Effect of human neural progenitor cells on injured spinal cord

To study whether human neural progenitor cells can differentiate into neural cells in vivo and improve the recovery of injured spinal cord in rats. Methods： Human neural progenitor cells were transplanted into the injured spinal cord and the functional recovery of the rats with spinal cord contusion injury was evaluated with Basso-Beattie-Bresnahan （ BBB ） locomotor scale and motor evoked potentials. Additionally, the differentiation of human neural progenitor cells was shown by immunocytochemistry. Results： Human neural progenitor cells developed into functional cells in the injured spinal cord and improved the recovery of injured spinal cord in both locomotor scores and electrophysiological parameters in rats. Conclusions ： Human neural progenitor cells can treat injured spinal cord, which may provide a new cell source for research of clinical application.