Mesenchymal stem cells from the bone marrow stroma: basic biology and potential for cell therapy

Mesenchymal stem cells (MSCs) can be isolated from the bone marrow stroma where they constitute an adult somatic stem cell population distinct from hemapoietic stem cells. MSCs are multipotent cells in that they have the capacity to generate progeny that can differentiate into multiple cell lineages. MSCs can be explanted in vitro from bone marrow aspirates and expanded in culture where they can be induced to terminally differentiate into osteoblasts, chrondrocytes, adipocytes, tenocytes and heamapoteic supporting tissue. This ability to differentiate has also been demonstrated in vivo following transplantation into rodents. Recent work has shown that MSCs may have a broader capacity for differentiation than was previously envisioned. In some circumstances, this increased potential for differentiation may make MSCs viable alternatives to embryonic stem cells. Accordingly, the multipotential capacity of MSCs, their accessible origin, and high ex vivo expansive potential, makes these cells attractive as tools for tissue engineering and cell-based therapy. This review will explore the basic biology of MSCs derived from adult tissues and consider their isolation, culture, and differentiation. In addition, we will examine some of the potential clinical applications of these cells and consider the future perspectives of their use.     

Allogeneic stem cell transplantation as immunotherapy for renal cell carcinoma: from immune enhancement to immune replacement

The lack of efficacy of chemotherapeutics, radiotherapy, and cytokine-based immunotherapy has catalyzed the preliminary enthusiasm for nonmyeloablative stem cell transplants as a novel investigational tool for treating metastatic RCC. The observation that cytokine-refractory metastatic RCC may regress following allogeneic transplantation attests to the powerful nature of the graft-versus-tumor effect that results from this treatment modality. Pilot trials and recent in vitro data provide the first clear evidence that the graft-versus-tumor effect mounted against RCC can produce clinically meaningful regression of a metastatic solid tumor. Given this observation, the authors have begun to expand the investigational use of nonmyeloablative stem cell transplants to other treatment-refractory genitourinary tumors, including metastatic bladder and prostate cancer. It is hoped that future demonstrations of graft-versus-tumor effects in other solid malignancies will lay the groundwork for the development of tumor-targeted strategies that use allogeneic transplantation of donor lymphocytes as an immunotherapeutic platform. Further advances in systemic and selective immunosuppressive agents that limit acute GVHD hold the potential to decrease the toxicity associated with nonmyeloablative stem cell transplants and may ultimately broaden the clinical applicability of this approach.     

Prostate cancer stem cell biology

The cancer stem cell (CSC) model provides insights into pathophysiology of cancers and their therapeutic response. The CSC model has been both controversial, yet provides a foundation to explore cancer biology. In this review, we provide an overview of CSC concepts, biology and potential therapeutic avenues. We then focus on prostate CSC including 1) their purported origin as either basal-derived or luminal-derived cells; 2) markers used for prostate CSC identification; 3) alterations of signaling pathways in prostate CSCs; 4) involvement of prostate CSCs in metastasis of PCa; and 5) microRNA-mediated regulation of prostate CSCs. Although definitive evidence for the identification and characterization of prostate CSCs still remains unclear, future directions pursuing therapeutic targets of CSCs may provide novel insights for the treatment of PCa.     

Lipofectamine介导转染神经干细胞的研究

目的观察阳离子脂质体法转染体外培养神经干细胞的转染效率和外源基因的表达。方法从1d龄新生鼠大脑皮层组织培养神经干细胞，带有报告基因GFP的穿梭质粒pAd．Tract-CMV经Lipofectamine介导转染神经干细胞后观察GFP表达，用流式细胞仪测定转染率。并观察阳离子脂质体对神经干细胞的毒性作用。结果荧光显微镜观察到被转染的神经干细胞长期表达绿色荧光蛋白。流式细胞仪结果显示转染率最高可达到39．99％。转染时，阳离子脂质体浓度超过24ml／L时表现出细胞毒性。结论阳离子脂质体hpofectamine介导转染神经干细胞效率较高，外源基因表达时间长。     

The adult neural stem cell niche: lessons for future neural cell replacement strategies

Transplantation of neural stem cells (NSCs) and the mobilization of endogenous neural precursors in the adult brain have been proposed as therapies for a wide range of central nervous system disorders, including neurodegenerative disease (eg, Parkinson's disease), demyelinating disorders (eg, multiple sclerosis), stroke, and trauma. Although there is great hope for the success of such therapies, the clinical development of NSC-based therapies is still in its infancy. A greater understanding of how to control the proliferation, migration, differentiation, and survival of NSCs and their progeny is critical for the development of cell replacement therapies. NSCs are partially regulated by the specialized microenvironment--or "niche"--in which these cells reside. The adult rodent brain retains NSCs in two separate niches that continually generate new neurons: the subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus subgranular zone (SGZ) of the hippocampus. Similar niches may be found in the human brain. In tis article, the authors briefly review their current understanding of the SVZ and SGZ niches. Lessons learned from these niches may allow one to manipulate NSCs better in culture for therapeutic transplantation and possibly even to mobilize endogenous precursors to repair diseased or injured brain.     

From pericytes to perivascular tumours: correlation between pathology,stem cell biology,and tissue engineering

Purpose

Pericytes were once thought only to aid in angiogenesis and blood pressure control. Gradually, the known functions of pericytes and other perivascular stem cells (PSC) have broadly increased. The following review article will summarize the known functions and importance of pericytes across disciplines of pathology, stem cell biology, and tissue engineering.

Methods

A literature review was performed for studies examining the importance of pericytes in pathology, stem cell biology, and tissue engineering.

Results

The importance of pericytes most prominently includes the identification of the perivascular identity of mesenchymal stem cells (or MSC). Now, pericytes and other PSC are known to display surface markers and multilineage differentiation potential of MSC. Accordingly, interest in the purification and use of PSC for mesenchymal tissue formation and regeneration has increased. Significant demonstration of in vivo efficacy in bone and muscle regeneration has been made in laboratory animals. Contemporaneously with the uncovering of an MSC identity for pericytes, investigators in tumour biology have found biologically relevant roles for pericytes in tumor formation, lymphovascular invasion, and perivascular tumor spread. As well, the contribution of pericytes to perivascular tumors has been examined (and debated), including glomus tumour, myopericytoma and solitary fibrous tumour/hemangiopericytoma. In addition, an expanding recognition of pericyte mimicry and perivascular tumour invasion has occurred, encompassing common malignancies of the brain and skin.

Conclusions

In summary, pericytes have a wide range of roles in health and disease. Pericytes are being increasingly studied for their role in tumour formation, growth and invasion. Likewise, the application of pericytes/PSC for mesenchymal tissue engineering is an expanding field of interest.     

Prostate stem cells: The niche and cell markers

Abstract:   Prostate cancer and benign prostatic hyperplasia are common diseases in elderly men worldwide. Identifying the prostate stem cell is an important tool to investigate the mechanism of these prostatic diseases. Although the prostate stem cell has not yet been detected, progress has been made. The 'niche' or place in which the prostate stem cell resides is thought to be located in the proximal region of the murine prostate, near the urethra. Several candidate prostate stem cell markers are currently under investigation. In this review, we summarize the historical approaches and recent evidence regarding the niche and prostate-specific stem cell markers.     

Neural stem cells and regeneration of injured spinal cord

Recent progress in the stem cell biology has led much insight into new therapeutic interventions aiming for the regeneration of the damaged central nervous system. The major strategies can be classified into two subgroups: (1) activation of endogenous neural stem cells, and (2) cell transplantation therapies. In either of these strategies, it is crucial to understand the underlying mechanisms of maintenance, activation, and differentiation of neural stem cells and subsequent process, including the migration, survival, and functional maturation of differentiated cells. In this paper, we would like to summarize our recent findings on the therapeutic interventions of the injured spinal cord, especially focusing on the development of treatment for the acute phase of spinal cord injury with anti-interleukin (IL)-6 receptor blocking antibody.     

Neural stem cells, neural progenitors, and neurotrophic factors

Neural stem cells (NSCs) have been proposed as a promising cellular source for the treatment of diseases in nervous systems. NSCs can self-renew and generate major cell types of the mammalian central nervous system throughout adulthood. NSCs exist not only in the embryo, but also in the adult brain neurogenic region: the subventricular zone (SVZ) of the lateral ventricle. Embryonic stem (ES) cells acquire NSC identity with a default mechanism. Under the regulations of leukemia inhibitory factor (LIF) and fibroblast growth factors, the NSCs then become neural progenitors. Neurotrophic and differentiation factors that regulate gene expression for controlling neural cell fate and function determine the differentiation of neural progenitors in the developing mammalian brain. For clinical application of NSCs in neurodegenerative disorders and damaged neurons, there are several critical problems that remain to be resolved: 1) how to obtain enough NSCs from reliable sources for autologous transplantation; 2) how to regulate neural plasticity of different adult stem cells; 3) how to control differentiation of NSCs in the adult nervous system. In order to understand the mechanisms that control NSC differentiation and behavior, we review the ontogeny of NSCs and other stem cell plasticity of neuronal differentiation. The role of NSCs and their regulation by neurotrophic factors in CNS development are also reviewed.     

脂肪干细胞体外诱导分化成神经细胞的研究

目的 观察脂肪干细胞( ADSCs)体外诱导分化成神经细胞的潜能,为恢复阴茎海绵体神经受损导致勃起功能障碍的研究建立基础.方法 取SD雄性大鼠脂肪组织进行原代培养.流式细胞仪检测ADSCs,体外诱导成脂肪细胞和神经细胞并进行鉴定.结果 ADSCs表面分子阳性率:CD44(+)96.4％、CD45(-)1.7％、CD34(-)0.9％.成脂细胞油红O染色脂滴染成红色.神经细胞荧光染色胶原纤维酸性蛋白(GFAP)、β-微管蛋白(β-tubulin)Ⅲ蛋白表达阳性,方法1[表皮生长因子(EGF)、碱性成纤维细胞生长因子(bFGF)、脑源性神经营养因子(BDNF)+吲哚美辛、胰岛素、3-异丁基-1-甲基黄嘌呤(IBMX)]和方法2(EGF、bFGF+吲哚美辛、胰岛素、IBMX)诱导率分别为(74.0±3.3)％、(65.3±2.1)％和(51.0±1.2)％、(41.0±1.1)％,且阳性细胞数差异有统计学意义(P＜0.01).结论 ADSCs在方法1作用下向神经细胞分化诱导率高,时间短;ADSCs可能成为治疗神经性勃起功能障碍的较理想干细胞.