Hematopoietic Stem Cell Homing to Injured Tissues

Centre for Cardiovascular Sciences, Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham, B15 2TT, UK.
Stem cell reviews (Impact Factor: 2.77). 02/2011; 7(3):672-82. DOI: 10.1007/s12015-011-9240-z
Source: PubMed

ABSTRACT The use of stem cells is considered a promising therapy for tissue regeneration and repair, particularly for tissues injured through degeneration, ischemia and inflammation. Bone marrow (BM)-derived haematopoietic stem cells (HSCs) are rare populations of multipotent stem cells that have been identified as promising potential candidates for treating a broad range of conditions. Although research into the use of stem cells for regenerative medicine is on a steep upward slope, clinical success has not been as forthcoming. This has been primarily attributed to a lack of information on the basic biology of stem cells, which remains insufficient to justify clinical studies. In particular, while our knowledge on the molecular adhesive mechanisms and local environmental factors governing stem cell homing to BM is detailed, our understanding of the mechanisms utilized at injured sites is very limited. For instance, it is unclear whether mechanisms used at injured sites are location specific or whether this recruitment can be modulated for therapeutic purposes. In addition, it has recently been suggested that platelets may play an important role in stem cell recruitment to sites of injury. A better understanding of the mechanisms used by stem cells during tissue homing would allow us to develop strategies to improve recruitment of these rare cells. This review will focus on the status of our current understanding of stem cell homing to injured tissues, the role of platelets and directions for the future.

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    • "The term cell homing describes the engrafted hematopoietic cells homing to bone marrow where they normally reside (Lapidot et al., 2005) or homing to the injury site (Kavanagh and Kalia, 2011). The hematopoietic cells in bone marrow can also be mobilized and home to other organs (Hopman and Dipersio, 2014). "
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    ABSTRACT: Regenerative endodontics has gained much attention in the past decade because it offers an alternative approach in treating endodontically involved teeth. Instead of filling the canal space with artificial materials, it attempts to fill the canal with vital tissues. The objective of regeneration is to regain the tissue and restore its function to the original state. In terms of pulp regeneration, a clinical protocol that intends to reestablish pulp/dentin tissues in the canal space has been developed-termed revitalization or revascularization. Histologic studies from animal and human teeth receiving revitalization have shown that pulp regeneration is difficult to achieve. In tissue engineering, there are 2 approaches to regeneration tissues: cell based and cell free. The former involves transplanting exogenous cells into the host, and the latter does not. Revitalization belongs to the latter approach. A number of crucial concepts have not been well discussed, noted, or understood in the field of regenerative endodontics in terms of pulp/dentin regeneration: (1) critical size defect of dentin and pulp, (2) cell lineage commitment to odontoblasts, (3) regeneration vs. repair, and (4) hurdles of cell-based pulp regeneration for clinical applications. This review article elaborates on these missing concepts and analyzes them at their cellular and molecular levels, which will in part explain why the non-cell-based revitalization procedure is difficult to establish pulp/dentin regeneration. Although the cell-based approach has been proven to regenerate pulp/dentin, such an approach will face barriers-with the key hurdle being the shortage of the current good manufacturing practice facilities, discussed herein.
    Journal of Dental Research 05/2014; 93(8). DOI:10.1177/0022034514537829 · 4.14 Impact Factor
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    • "Therefore, an embryonic murine HSC line, HPC-7, were used and were kindly given as a gift from Professor L. Carlsson, Umea University, Sweden. These cells (HPC-7) have been used extensively in published studies [20], [29], [53], [54], [55], [56]. HPC-7 are an immortalised SC line generated by transfection with the LIM-homeobox gene, Lhx2, into murine embryonic SCs [56]. "
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    ABSTRACT: Renal disease affects over 500 million people worldwide and is set to increase as treatment options are predominately supportive. Evidence suggests that exogenous haematopoietic stem cells (HSCs) can be of benefit but due to the rarity and poor homing of these cells, benefits are either minor or transitory. Mechanisms governing HSC recruitment to injured renal microcirculation are poorly understood; therefore this study determined (i) the adhesion molecules responsible for HSC recruitment to the injured kidney, (ii) if cytokine HSC pre-treatment can enhance their homing and (iii) the molecular mechanisms accountable for any enhancement. Adherent and free-flowing HSCs were determined in an intravital murine model of renal ischaemia-reperfusion injury. Some HSCs and animals were pre-treated prior to HSC infusion with function blocking antibodies, hyaluronidase or cytokines. Changes in surface expression and clustering of HSC adhesion molecules were determined using flow cytometry and confocal microscopy. HSC adhesion to endothelial counter-ligands (VCAM-1, hyaluronan) was determined using static adhesion assays in vitro. CD49d, CD44, VCAM-1 and hyaluronan governed HSC adhesion to the IR-injured kidney. Both KC and SDF-1α pre-treatment strategies significantly increased HSC adhesion within injured kidney, whilst SDF-1α also increased numbers continuing to circulate. SDF-1α and KC did not increase CD49d or CD44 expression but increased HSC adhesion to VCAM-1 and hyaluronan respectively. SDF-1α increased CD49d surface clustering, as well as HSC deformability. Increasing HSC adhesive capacity for its endothelial counter-ligands, potentially through surface clustering, may explain their enhanced renal retention in vivo. Furthermore, increasing HSC deformability through SDF-1α treatment could explain the prolonged systemic circulation; the HSC can therefore continue to survey the damaged tissue instead of becoming entrapped within non-injured sites. Therefore manipulating these mechanisms of HSC recruitment outlined may improve the clinical outcome of cellular therapies for kidney disease.
    PLoS ONE 06/2013; 8(6):e66489. DOI:10.1371/journal.pone.0066489 · 3.23 Impact Factor
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    • "HSCs show self-renewal, mobilization, and multipotent differentiation capacities, as they are able to give rise to the myeloid (including monocytes and macrophages) and lymphoid cells, replenishing all blood cell types, and providing homeostasis of blood cells (Sieburg et al., 2011). HSCs are also able to home to the damaged sites (Kavanagh and Kalia, 2011). HSC transplantation has gained much consideration as therapy for hematological malignancies and for the treatment of severe autoimmune diseases (Muraro and Uccelli, 2010). "
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    ABSTRACT: Autism and autism spectrum disorders (ASDs) are heterogeneous, severe neuro-developmental disorders with core symptoms of dysfunctions in social interactions and communication skills, restricted interests, repetitive - stereotypic verbal and non-verbal behaviors. Biomolecular evidence points to complex gene-environmental interactions in ASDs. Several biochemical processes are associated with ASDs: oxidative stress (including endoplasmic reticulum stress), decreased methylation capacity, limited production of glutathione; mitochondrial dysfunction, intestinal dysbiosis, increased toxic metal burden, and various immune abnormalities. The known immunological disorders include: T-lymphocyte populations and function, gene expression changes in monocytes, several autoimmune-related findings, high levels of N-acetylgalactosaminidase (which precludes macrophage activation), and primary immune deficiencies. These immunological observations may result in minicolumn structural changes in the brain, as well as, abnormal immune mediation of synaptic functions. Equally, these immune dysregulations serve as the rationale for immune-directed interventions such as hematopoietic stem cells (HSCs), which are pivotal in controlling chronic inflammation and in the restoration of immunological balance. These properties make them intriguing potential agents for ASD treatments. This prospective review will focus on the current state-of-the-art knowledge and challenges intrinsic in the application of HSCs for ASD-related immunological disorders.
    Frontiers in Immunology 06/2013; 4:140. DOI:10.3389/fimmu.2013.00140
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