Mesenchymal Stem Cells - Basics and Clinical Application II

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However, when scientists extract the inner cell mass and grow these cells in special laboratory conditions, they retain the properties of embryonic stem cells. These cells are incredibly valuable because they provide a renewable resource for studying normal development and disease, and for testing drugs and other therapies.

Human embryonic stem cells have been derived primarily from blastocysts created by in vitro fertilization IVF for assisted reproduction that were no longer needed. Typically, these stem cells can generate different cell types for the specific tissue or organ in which they live.

Some tissues and organs within your body contain small caches of tissue-specific stem cells whose job it is to replace cells from that tissue that are lost in normal day-to-day living or in injury, such as those in your skin, blood, and the lining of your gut. However, study of these cells has increased our general knowledge about normal development, what changes in aging, and what happens with injury and disease.

The first MSCs were discovered in the bone marrow and were shown to be capable of making bone, cartilage and fat cells. Since then, they have been grown from other tissues, such as fat and cord blood. See if you have enough points for this item. Sign in.

Human mesenchymal stem cells: from basic biology to clinical applications | Gene Therapy

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Alessandro Plebani. The Blood Brain Barrier and Inflammation. Cells originating from the endothelial, mesenchymal, and adipose tissue can be distinguished[ 7 - 9 ]. In addition to the bone marrow, mesenchymal stem cells can be isolated from a wide variety of tissues adipose tissue, peripheral blood, placenta, dental pulp, synovial membrane, periodontal ligaments, endometrial, trabecular and compact bones. Under appropriate culture conditions they can mature to mesodermal, endodermal, and ectodermal cells.

They can be used safely to aid tissue regeneration because they do not form teratomas[ 10 - 14 ]. Adult stem cells play a prominent role in local tissue repair and regeneration. Based on ethical considerations, the isolation and therapeutic use of adult stem cells, in contrast to embryonic stem cells, is significantly more favorable.

On the other hand, adult stem cells are also available from autograft, thereby substantially eliminating the risk of tissue rejection[ 6 ]. Adult stem cells are essential creators of both single- and multilayered epithelium[ 6 , 14 - 17 ]. Within the heterogeneous cancer cell population hierarchy, it is believed that only a specific set of cancer stem cells, specifically self-renewing, pluripotent tumor-initiating, and repopulating cells have a direct tumor and metastasis-promoting property.

In malignant tumors, these cells contribute greatly to the development of resistance against cell death, uncontrolled proliferation, aggressive spread, and resistance to conventional therapies.

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Tumor stem cells stimulate cancer cell dormancy and initiate relapse. Initially it was hypothesized that tumor stem cells were derived from normal stem cells. However, recent studies have shown that progenitor cells on genetic e. Tumor stem cells are not necessarily descendants of normal progenitors or stem cells. Tumor stem cells may also be formed as a result of cell fusion between normal stem cells and somatic cells[ 6 , 18 , 19 ]. Due to their long lifetime, cancer cells accumulate many mutations essential for malignant transformation. Although cancer cells are predominantly derived from oncogenic transformed aberrant adult stem cells, epithelial-mesenchymal transition also facilitates the transdifferentiation mechanism of cancer cells to acquire stem cell-like properties.

In the early spread of preinvasive tumors, epithelial-mesenchymal transition is of paramount importance. Due to mesenchymal-epithelial transition changes the second phenotypic status of the cancer cells contributes to metastasis formation[ 20 - 24 ]. Like normal adult stem cells, metastatic cancer cells can enter a dormant state because of inhibitors from microenvironmental signals or in the absence of appropriate stimulating signals. At the same time, the nonproliferative, dormant phenotype of cancer cells from different primary tumors can be overwritten by the microenvironmental properties i.

From a therapeutic point of view, it is possible to induce differentiation of cancer cells before and during chemotherapy. While this strategy can be effective in treating hematological cancers e. These cells are artificially created from nonpluripotent cells. They are typically generated from mature somatic cells by the induction of genes that determine the stem cell phenotype[ 25 ].

In many respects such as expression of stem cell specific genes and proteins, chromatin methylation pattern, cell duplication time, creation of embryo-like body, formation of teratomas and viable chimeras these cells are similar to natural pluripotent stem cells, such as embryonic stem cells[ 25 - 27 ]. The emergence of human induced pluripotent stem cells is an important step in stem cell research, as the method allows the development of pluripotent stem cells without sacrificing of embryos, graft-versus-host disease, and immunological rejection. Induced pluripotent stem cells have already been used for drug development and modeling of many diseases and will be beneficial in transplant medicine[ 25 - 27 ].

However, induced pluripotent stem cells may also present a risk that may limit their clinical use. Genetically modified adult cells may increase expression of protumor genes and oncogenes. There are, however, methods that can eliminate oncogenes after induction of pluripotence and even induce pluripotent stem cells without genetic alteration of adult stem cells so-called protein-induced pluripotent stem cells [ 25 - 28 ].

From a clinical and research point of view, stem cells can be used for drug research and toxicity studies, development and gene regulation studies, genetic modification of laboratory and farm animals i. In terms of their clinical applicability including in autoimmune disorders, cell replacement procedures and therapies that alter the natural course of diseases should be considered. The idea of using stem cells as a paradigm for replacing damaged tissues with impaired function was first introduced after World War II.

Essentially, experiments that led to the fight against radiation injury were the basis for the practical applicability of stem cells.