Altered Erythro-Myeloid Progenitor Cells Are Highly Expanded in Intensively Regenerating Hematopoiesis (original) (raw)

Mechanisms of Cell Regeneration — From Differentiation to Maintenance of Cell Phenotype

Cells and Biomaterials in Regenerative Medicine, 2014

In adult organisms the regenerative capacity of certain organs or tissues can be limited, resulting in an important clinical challenge for physicians and scientists [1-3]. Regeneration involves the capacity for renewal or recomposition of tissues, organs or even organisms, after considerable physical injury or damage, resulting from pathologies, tumors, congenital diseases or traumas, for example. As a consequence of tissue regeneration, both the composition and the tissue properties are restored, and the newly formed tissue is highly similar to the original tissue. The regenerative capacity is directly related to the presence of stem cells or progenitor cells, which are capable of proliferation and differentiation [4,5]. Tissues that maintain a high proliferative capacity, such as the hematopoietic system, have regenerative capacity even in adult organisms [6]. Cell proliferation occurs in repair processes in general, accompanied by intense production of extracellular matrix, with large amounts of collagen, resulting in the formation of fibrous tissue to occupy the injured area. Although there is lesion filling, both the composition and the tissue properties are different from the original tissue, and the tissue organization pattern is not restored, leading to an altered performance of its functions [2]. Skin healing processes with the presence of scars are examples of tissue repair [3]. Besides the natural processes of regeneration and repair, it is possible, through medical intervention, to fill lesions with natural or synthetic materials, aiming at the recovery of the

Stretching the limits: Stem cells in regeneration science

Developmental Dynamics, 2008

The focus of regenerative medicine is rebuilding damaged tissues by cell transplantation or implantation of bioartificial tissues. In either case, therapies focus on adult stem cells (ASCs) and embryonic stem cells (ESCs) as cell sources. Here we review four topics based on these two cell sources. The first compares the current performance of ASCs and ESCs as cell transplant therapies and the drawbacks of each. The second explores somatic cell nuclear transfer (SCNT) as a method to derive ESCs that will not be immunorejected.

Comparative regenerative mechanisms across different mammalian tissues

NPJ Regenerative medicine, 2018

Stimulating regeneration of complex tissues and organs after injury to effect complete structural and functional repair, is an attractive therapeutic option that would revolutionize clinical medicine. Compared to many metazoan phyla that show extraordinary regenerative capacity, which in some instances persists throughout life, regeneration in mammalians, particularly humans, is limited or absent. Here we consider recent insights in the elucidation of molecular mechanisms of regeneration that have come from studies of tissue homeostasis and injury repair in mammalian tissues that span the spectrum from little or no self-renewal, to those showing active cell turnover throughout life. These studies highlight the diversity of factors that constrain regeneration, including immune responses, extracellular matrix composition, age, injury type, physiological adaptation, and angiogenic and neurogenic capacity. Despite these constraints, much progress has been made in elucidating key molecul...

Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs)

Journal of Cellular and Molecular Medicine, 2010

In this review, we focus on the adult stem/progenitor cells that were initially isolated from bone marrow and first referred to as colony forming units-fibroblastic, then as marrow stromal cells and subsequently as either mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs). The current interest in MSCs and similar cells from other tissues is reflected in over 10,000 citations in PubMed at the time of this writing with 5 to 10 new publications per day. It is also reflected in over 100 registered clinical trials with MSCs or related cells (http//www.clinicaltrials.gov). As a guide to the vast literature, this review will attempt to summarize many of the publications in terms of three paradigms that have directed much of the work: an initial paradigm that the primary role of the cells was to form niches for haematopoietic stem cells (paradigm I); a second paradigm that the cells repaired tissues by engraftment and differentiation to replace injured cells (paradigm II); and the more recent paradigm that MSCs engage in cross-talk with injured tissues and thereby generate microenvironments or 'quasi-niches' that enhance the repair tissues (paradigm III).

Regenerative Biology and Medicine

Journal of musculoskeletal & neuronal interactions

The replacement of damaged tissues and organs with tissue and organ transplants or bionic implants has serious drawbacks. There is now emerging a new approach to tissue and organ replacement, regenerative biology and medicine. Regenerative biology seeks to understand the cellular and molecular differences between regenerating and non-regenerating tissues. Regenerative medicine seeks to apply this understanding to restore tissue structure and function in damaged, non-regenerating tissues. Regeneration is accomplished by three mechanisms, each of which uses or produces a different kind of regenerationcompetent cell. Compensatory hyperplasia is regeneration by the proliferation of cells which maintain all or most of their differentiated functions (e.g., liver). The urodele amphibians regenerate a variety of tissues by the dedifferentiation of mature cells to produce progenitor cells capable of division. Many tissues contain reserve stem or progenitor cells that are activated by injury to restore the tissue while simultaneously renewing themselves. All regeneration-competent cells have two features in common. First, they are not terminally differentiated and can re-enter the cell cycle in response to signals in the injury environment. Second, their activation is invariably accompanied by the dissolution of the extracellular matrix (ECM) surrounding the cells, suggesting that the ECM is an important regulator of their state of differentiation. Regenerative medicine uses three approaches. First is the transplantation of cells into the damaged area. Second is the construction of bioartificial tissues by seeding cells into a biodegradable scaffold where they produce a normal matrix. Third is the use of a biomaterial scaffold or drug delivery system to stimulate regeneration in vivo from regeneration-competent cells. There is substantial evidence that non-regenerating mammalian tissues harbor regeneration-competent cells that are forced into a pathway of scar tissue formation. Regeneration can be induced if the factors leading to scar formation are inhibited and the appropriate signaling environment is supplied. An overview of regenerative mechanisms, approaches of regenerative medicine, research directions, and research issues will be given.