Clinical Impact of Circulating CD34-Positive Cells on Bone Regeneration and Healing

Abstract

Failures in fracture healing after conventional autologous and allogenic bone grafting are mainly due to poor vascularization. To meet the clinical demand, recent attentions in the regeneration and repair of bone have been focused on the use of stem cells such as bone marrow mesenchymal stem cells and circulating skeletal stem cells. Circulating stem cells are currently paid a lot of attention due to their ease of clinical setting and high potential for osteogenesis and angiogenesis. In this report, we focus on the first proof-of-principle experiments demonstrating the collaborative characteristics of circulating CD34(+) cells, known as endothelial and hematopoietic progenitor cell-rich population, which are capable to differentiate into both endothelial cells and osteoblasts. Transplantation of circulating CD34(+) cells provides a favorable environment for fracture healing via angiogenesis/vasculogenesis and osteogenesis, finally leading to functional recovery from fracture. Based on a series of basic studies, we performed a phase 1/2 clinical trial of autologous CD34(+) cell transplantation in patients with tibial or femoral nonunions and reported the safety and efficacy of this novel therapy. In this review, the current concepts and strategies in circulating CD34(+) cell-based therapy and its potential applications for bone repair will be highlighted.

Involvement of serum‐derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone‐related proteins

“…Another study demonstrated that mechanical tensile strain using a four‐point bending device promoted integrin β 1 ‐mediated Wnt/β‐catenin nuclear translocation, which induced the expression of an osteoblastic transcriptional factor, osterix (Kobayashi, Uehara, Udagawa & Takahashi, 2016). CD34 mediates the attachment of stem cells to the bone marrow ECM or directly to stromal cells; circulating CD34 + cells are capable of differentiating into osteoblasts (Kuroda et al., 2014). Furthermore, the integrin β 1 /Shc association leads to the activation of extracellular signal‐regulated kinase (ERK), which is critical for shear induction of bone formation‐related genes in osteoblast‐like cells (Lee et al., 2008).…”

Stem cell-based approaches in dentistry

“…They could be directly derived from dental tissues (e.g., pulp, periodontium), but a contribution from blood-derived circulating MSCs has not to be excluded. Indeed, MSCs are found in the circulation and are likely to engraft in all tissues of the body (Kuroda et al, 2014;Lemoli et al, 2006). The embryonic origins of circulating MSCs are different from those of DMSCs (La Noce et al, 2014;Pagella et al, 2015), thus suggesting distinct properties and functions for these two stem cell populations.…”

Enhanced osteoblastic differentiation and bone formation in co-culture of human bone marrow mesenchymal stromal cells and peripheral blood mononuclear cells with exogenous VEGF

“…Bone marrow (BM) derived mesenchymal stromal cells (MSCs) are an attractive cell source for osteoprogenitors [1], but angiogenesis is central in bone development and fracture healing, as well as in graft survival after implantation [1,2]. Therefore, the synergistic crosstalk between MSCs and endothelial cells, influencing both angiogenesis and osteogenesis, has gained interest as a potential solution for improved bone tissue engineered therapies.…”