Assessment of umbilical cord tissue as a source of mesenchymal stem cell/endothelial cell mixtures for bone regeneration

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From: Regenerative Medicine(Vol. 8, Issue 5)
Publisher: Future Medicine Ltd.
Document Type: Report
Length: 7,633 words
Lexile Measure: 1470L

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Author(s): Dimitrios Kouroupis 1 , Sarah M Churchman 1 , Anne English 1 , Paul Emery 1 , Peter V Giannoudis 1 , Dennis McGonagle 1 , Elena A Jones [*] 2



bone marrow; bone regeneration; endothelial cells; mesenchymal stem cells; umbilical cord

Bone regeneration following fracture or tumor resection is highly challenging, and bone grafting procedures remain the gold standard therapeutic intervention [1] . Autologous grafts, however, possess numerous disadvantages including donor site morbidity and associated pain [2] . Bone marrow (BM) mesenchymal stem cells (MSCs) were first used in combination with osteoconductive scaffolds to repair bone [3,4] . Additionally, systemic administration of BM MSCs has been used in both autologous and allogeneic settings to treat osteogenesis imperfecta [5] . BM MSCs were also the first type of MSCs shown to possess immunoregulatory capacity [6] , leading to worldwide therapeutic use for the treatment of graft-versus-host disease [7] .

BM MSCs are relatively easy to procure, although their rarity in BM aspirates (0.001-0.01%) necessitates culture amplification in order to achieve the required number of cells for therapy [8] . However, extended MSC passaging is to be avoided owing to the loss of potency and concerns relating to a potential for accumulating senescent cells and chromosomal abnormalities [9,10] . With these issues in mind, MSCs of perinatal origin have attracted increased interest as potential candidates for bone repair applications. Umbilical cord (UC) tissue, UC blood, fetal liver, villous placenta, fetal membranes and amniotic fluid have all been shown to host MSCs [11-14] . Human UC tissue in particular represents an attractive MSC source for bone regeneration [15] ; this is not only because their harvest is noninvasive, but also because of their juvenile biological age, which argues for a lower possibility of genetic alterations [14] . However, controversy still exists regarding the osteogenic capacity of UC MSCs in comparison to BM MSCs. Early studies showed that UC MSCs could in principle differentiate towards osteoblasts [16-19] , however, later studies documented that UC MSCs were only weakly osteogenic [20,21] . These discrepancies could be explained by the fact that UC MSC cultures in the aforementioned studies were derived from different locations within the UC tissue [22] . The inner tissue architecture of UC is comprised of two arteries and one vein, which are surrounded by a matrix of mucous connective tissue, termed Wharton's jelly [23] . MSCs derived from perivascular and Wharton's jelly areas, in particular, may have different propencities for osteogenesis [18,20] .

It should be kept in mind that bone formation in vivo is mediated by MSCs that closely interact with local vasculature [24] ; and normally, endothelial cells (ECs) crosstalk with adjacent MSCs in their periendothelial niche [25,26] , and influence MSC behavior in situ . In physiological bone repair processes, newly synthesized vessels are stabilized by MSCs and anastomose with pre-existing vessels, therefore long-lasting, functional regeneration of truly vascularized bone is now believed to require both cell sources [27-29] . Minimally manipulated BM isolates, containing autologous MSCs and potentially ECs, have been successfully used in orthopedic settings [30,31] . The advantage of using UC tissue in this context would be the coexistence of both...

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Gale Document Number: GALE|A341806673