Minimally manipulated whole human umbilical cord is a rich source of clinical-grade human mesenchymal stromal cells expanded in human platelet lysate

Capelli, Chiara; Gotti, Elisa; Morigi, Marina; Rota, Cinzia; Weng, Ling; Dazzi, Francesco; Spinelli, Orietta; Cazzaniga, Giovanni; Trezzi, Rosangela; Gianatti, Andrea; Rambaldi, Alessandro; Golay, Joseé; Introna, Martino

doi:10.3109/14653249.2011.563294

Cited by 107 publications

(85 citation statements)

References 52 publications

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“…+++ [7] HOX-gene [7] , DLK-1 [16] , pSmad2 (low and modulated) [12] Negative for: CD14, CD34 [1] , CD56 [7] UC-MSC Positive for: CD90, CD73, CD105, CD13, CD44 [1] PAI-1, MnSOD [10] , HOX-gene (different expression pattern) [7] Reports for adipo- [13,15] and osteogenic [7,12] differentiation failure CD56, CD146…”

Section: Discussionmentioning

confidence: 99%

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Umbilical cord fibroblasts: Could they be considered as mesenchymal stem cells?

Zeddou¹

2014

WJSC

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In cell therapy protocols, many tissues were proposed as a source of mesenchymal stem cells (MSC) isolation. So far, bone marrow (BM) has been presented as the main source of MSC despite the invasive isolation procedure related to this source. During the last years, the umbilical cord (UC) matrix was cited in different studies as a reliable source from which long term ex vivo proliferating fibroblasts were isolated but with contradictory data about their immunophenotype, gene expression profile, and differentiation potential. Hence, an interesting question emerged: Are cells isolated from cord matrix (UC-MSC) different from other MSCs? In this review, we will summarize different studies that isolated and characterized UC-MSC. Considering BM-MSC as gold standard, we will discuss if UC-MSC fulfill different criteria that define MSC, and what remain to be done in this issue.

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Section: Discussionmentioning

confidence: 99%

“…Human UC-MSC did not express BSP, which can account for their inability to differentiate into osteoblasts [7] . UC-MSCs were also shown to differentiate into adipocytes in a very limited manner [13,15] . Adipogenic potential Zeddou M et al .…”

Section: Uc-mscs Differentiation Potentialmentioning

confidence: 99%

Umbilical cord fibroblasts: Could they be considered as mesenchymal stem cells?

Zeddou¹

2014

WJSC

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“…Moreover, BM-MSCs are adult stem cells with lower proliferation capacity compared with other MSCs originating from fetal tissues [5]. The umbilical cord (UC) can be a source of highly proliferating fetal MSCs [6,7] that are more easily collectable than BM-MSCs. UC-MSCs are isolated from Wharton's Jelly, representing a noncontroversial source of fetal stem cells [8].…”

mentioning

confidence: 99%

“…In this context, we prepared clinical-grade UC-MSCs [6], and we investigated if UC-MSCs could be used as substitutes for BM-MSCs in musculoskeletal regeneration. UCMSCs clearly display typical MSC features as defined by the International Society for Cellular Therapy [17].…”

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confidence: 99%

Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the In Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration

Todeschi

Backly

Capelli

et al. 2015

Stem Cells and Development

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Umbilical cord mesenchymal stem cells (UC-MSCs) show properties similar to bone marrow mesenchymal stem cells (BM-MSCs), although controversial data exist regarding their osteogenic potential. We prepared clinical-grade UC-MSCs from Wharton's Jelly and we investigated if UC-MSCs could be used as substitutes for BM-MSCs in muscoloskeletal regeneration as a more readily available and functional source of MSCs. UCMSCs were loaded onto scaffolds and implanted subcutaneously (ectopically) and in critical-sized calvarial defects (orthotopically) in mice. For live cell-tracking experiments, UC-MSCs were first transduced with the luciferase gene. Angiogenic properties of UC-MSCs were tested using the mouse metatarsal angiogenesis assay. Cell secretomes were screened for the presence of various cytokines using an array assay. Analysis of implanted scaffolds showed that UC-MSCs, contrary to BM-MSCs, remained detectable in the implants for 3 weeks at most and did not induce bone formation in an ectopic location. Instead, they induced a significant increase of blood vessel ingrowth. In agreement with these observations, UC-MSC-conditioned medium presented a distinct and stronger proinflammatory/chemotactic cytokine profile than BM-MSCs and a significantly enhanced angiogenic activity. When UC-MSCs were orthotopically transplanted in a calvarial defect, they promoted increased bone formation as well as BM-MSCs. However, at variance with BM-MSCs, the new bone was deposited through the activity of stimulated host cells, highlighting the importance of the microenvironment on determining cell commitment and response. Therefore, we propose, as therapy for bone lesions, the use of allogeneic UC-MSCs by not depositing bone matrix directly, but acting through the activation of endogenous repair mechanisms.

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“…MSCs derived from the umbilical cord have a significant advantage over those derived from bone marrow, placenta, or other tissues, as hUC-MSCs are easy to acquire and culture, and the cells have a high proliferation rate (32) and low immunogenicity (33). Moreover, hUC-MSCs are not tumorigenic and will not give rise to teratomas (34,35), and thus overall, fewer bioethical issues are involved in their collection or use (36). Low immunogenicity immunoregulation (33,35,37), paracrine signaling, migration and the genomic stability of hUC-MSCs (38) have made them ideal candidates for therapies and favorable clinical prospects.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of human umbilical cord-derived mesenchymal stems cells for the treatment of Becker muscular dystrophy in affected pedigree members

Pang

Cui

Zhang

et al. 2015

International Journal of Molecular Medicine

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Abstract. The regeneration of muscle tissue has been achieved using multipotent mesenchymal stem cells in mouse models of injured skeletal muscle. In the present study, the utility of multipotent human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in the treatment of Becker muscular dystrophy (BMD), a genetic disease where muscle tissue fails to regenerate, was examined in members from a pedigree affected by BMD. The disease status was evaluated in 4 affected pedigree members (II1, II2, II3 and III2; aged 50, 46, 42 and 6 years, respectively). The transplantation of the hUC-MSCs (performed on 3 patients, I2, II3 and III2) was performed by infusion with an intravenous drip over a 30-min period, and the patients were evaluated at 1, 3, 4 and 12 weeks following the procedure. The evaluation was based on physical characteristics, as well as on molecular testing for serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels and a histological examination of muscle biopsies. The patients suffered no adverse reactions in response to the transplantation of the hUC-MSCs. At 1 week following transplantation all 3 patients showed improvement in the muscle force of the limbs, muscle size and daily activity. The walking gait of patient III2 had improved by 1 week post-transplantation and reached a normal status by 12 weeks. Serum CK and LDH levels were decreased relative to the baseline levels. A histological examination of muscle biopsies displayed no obvious tissue regeneration. In conclusion, the treatment of patients with BMD using hUC-MSCs was safe and of therapeutic benefit that lasted for up to 12 weeks. hUC-MSCs are, therefore, a potential cell therapy-based treatment option for patients with muscular dystrophies.

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Minimally manipulated whole human umbilical cord is a rich source of clinical-grade human mesenchymal stromal cells expanded in human platelet lysate

Cited by 107 publications

References 52 publications

Umbilical cord fibroblasts: Could they be considered as mesenchymal stem cells?

Umbilical cord fibroblasts: Could they be considered as mesenchymal stem cells?

Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the In Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration

Transplantation of human umbilical cord-derived mesenchymal stems cells for the treatment of Becker muscular dystrophy in affected pedigree members

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