Human Umbilical Cord Blood-Derived CD34+ Cells Reverse Osteoporosis in NOD/SCID Mice by Altering Osteoblastic and Osteoclastic Activities

Abstract

Background Osteoporosis is a bone disorder associated with loss of bone mineral density and micro architecture. A balance of osteoblasts and osteoclasts activities maintains bone homeostasis. Increased bone loss due to increased osteoclast and decreased osteoblast activities is considered as an underlying cause of osteoporosis. Methods and Findings The cures for osteoporosis are limited, consequently the potential of CD34+ cell therapies is currently being considered. We developed a nanofiber-based expansion technology to obtain adequate numbers of CD34 + cells isolated from human umbilical cord blood, for therapeutic applications. Herein, we show that CD34 + cells could be differentiated into osteoblastic lineage, in vitro . Systemically delivered CD34 + cells home to the bone marrow and significantly improve bone deposition, bone mineral density and bone micro-architecture in osteoporotic mice. The elevated levels of osteocalcin, IL-10, GM-CSF, and decreased levels of MCP-1 in serum parallel the improvements in bone micro-architecture. Furthermore, CD34 + cells improved osteoblast activity and concurrently impaired osteoclast differentiation, maturation and functionality. Conclusions These findings demonstrate a novel approach utilizing nanofiber-expanded CD34 + cells as a therapeutic application for the treatment of osteoporosis.

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

“…suffering from osteoporosis [21]. Largely due to the influence of multiple osteogenetic signals, which are specialized for the proliferation and differentiation of osteoblasts, an increase in the number of osteoblasts results from the mesenchymal progenitor cells [2]. The objective of the current study was to elucidate the correlation between LINC00311 and DLL3 from an osteoporosis perspective.…”

“…Over 200 million people worldwide suffer from osteoporosis [2]. Postmenopausal women represent the more likely group, compared with their male counterparts, to be diagnosed with the condition, with a greater prevalence of the disorder strongly correlated with increasing age [3].…”

“…The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) has been regarded as an essential factor in the regulation of a variety of physiological and pathophysiological processes including that of osteoporosis [6]. Bone homeostasis is maintained by a tight balance between osteoblast and osteoclast activity, with increased activity leading to bone loss and potentially causing osteoporosis [2]. Osteoblast differentiation is associated with the incidence of osteoporosis, with studies implicating long non-coding RNA (LncRNA) as a factor in the condition [7].…”

The hematopoietic system in the context of regenerative medicine

“…A number of new procedures have been attempted to achieve this goal, including various cytokine cocktails [158–160], novel matrices such as nanofibers [161–163], copper chelating agents [164, 165], transcriptional activators and inhibitors [166–176], and feeder layers often consisting of MSC and/or endothelial cells [177–183]. While these methods have all demonstrated that it is possible to significantly expand committed progenitor cells in vitro, with the exception of studies employing a feeder layer [177–183] (which would obviously complicate translation to the clinical arena), the ability to expand true long-term repopulating HSC present within UCB remains an elusive target [184–186] that is the subject of intense investigation, with recent advances suggesting this goal could be achieved in the near future [187].…”

Nanofiber-expanded human umbilical cord blood-derived CD34+ cell therapy accelerates murine cutaneous wound closure by attenuating pro-inflammatory factors and secreting IL-10

“…Thus, ex-vivo expansion of progenitor cells has become recognized as a critically important step in translation to the clinic. Our ex vivo expansion technology provides a sufficient number of progenitor cells for preclinical evaluations, and expanded cells have been found to be biologically functional in various ischemic and degenerative models (Aggarwal et al, 2012; Das et al, 2009a,b). However, their potential uses for wound healing and their underlying mechanisms of action have yet to be established.…”