Human umbilical cord derivatives regenerate intervertebral disc

Abstract

Intervertebral disc (IVD) degeneration is characterized by the loss of nucleus pulposus (NP), which is a common cause for lower back pain. Although, currently, there is no cure for the degenerative disc disease, stem cell therapy is increasingly being considered for its treatment. In this study, we investigated the feasibility and efficacy of human umbilical cord mesenchymal stem cells (MSCs) and chondroprogenitor cells (CPCs) derived from those cells to regenerate damaged IVD in a rabbit model. Transplanted cells survived, engrafted and dispersed into NP in situ. Significant improvement in the histology, cellularity, extracellular matrix proteins, and water and glycosaminoglycan contents in IVD recipients of CPCs was observed compared to MSCs. In addition, IVDs receiving CPCs exhibited higher expression of NP-specific human markers, SOX9, aggrecan, collagen 2, FOXF1 and KRT19. The novelty of the study is that in vitro differentiated CPCs derived from umbilical cord MSCs, demonstrated far greater capacity to regenerate damaged IVDs, which provides basis and impetus for stem cell based clinical studies to treat degenerative disc disease.

Mesenchymal stem cells: Cell therapy and regeneration potential

“…Stem cell‐based therapies can greatly impact the field of regenerative medicine. MSCs have been used in preclinical and clinical studies to treat degenerative diseases, such as AD (Cui et al, ; Han et al, ; J. Shin et al, ; X. Wang, Ma, et al, ), DDD (Ahn et al, ; Beeravolu et al, ; Pereira et al, ; Perez‐Cruet et al, ), MS (Harris et al, ; Nasri et al, ; Planchon et al, ), PD (Jamali et al, ; H. Kim, Lee, et al, ), and RDD (Mead, Amaral, & Tomarev, ), as summarized in Table . The regenerative mechanisms of transplanted MSCs for these diseases are still unclear; however, some reports have suggested that MSCs have the potential to differentiate or have paracrine effects in vivo (Lee, Choi, Cha, & Hwang, ).…”

“…The regenerative mechanisms of transplanted MSCs for these diseases are still unclear; however, some reports have suggested that MSCs have the potential to differentiate or have paracrine effects in vivo (Lee, Choi, Cha, & Hwang, ). Our recent preclinical studies showed that nucleus pulposus‐like cells (NPCs) derived from MSCs were more efficacious than MSCs in a rabbit model of DDD (Beeravolu et al, ; Perez‐Cruet et al, ). The transplanted MSC‐derived NPCs survived, migrated, and integrated in the nucleus pulposus (NP) of the intervertebral discs (IVDs).…”

“…MSCs have shown promising outcomes in preclinical and clinical studies for treating pain and degenerative diseases such as AD, DDD, MS, PD, and RDD and providing immunomodulatory, neuroprotective, and anti‐inflammatory responses in vivo (Beeravolu et al, ; Ding, Kumar, & Mok, ; Gugliandolo, Bramanti, & Mazzon, ; Nasri et al, ; Osborne, Sanderson, & Martin, ; Perez‐Cruet et al, ; Turgeman, ; van Buul et al, ; R. Zhang, Liu, et al, ). Studies have shown that MSCs can be differentiated to NPCs to regenerate the NP in the IVD and to retinal progenitor cells to regenerate the retina within the eye (Beeravolu et al, ; Ding et al, ; Perez‐Cruet et al, ). Furthermore, MSCs have the ability to exert an anti‐inflammatory and immunomodulatory response (R. Zhang, Liu, et al, ).…”

“…MSCs have been used in preclinical and clinical studies to treat degenerative diseases, such as AD (Cui et al, 2017;Han et al, 2018;X. Wang, Ma, et al, 2018), DDD (Ahn et al, 2015;Beeravolu et al, 2018;Pereira et al, 2016;Perez-Cruet et al, 2018), MS (Harris et al, 2018;Nasri et al, 2018;Planchon et al, 2018), PD (Jamali et al, 2018;H. Kim, Lee, et al, 2018), and RDD (Mead, Amaral, & Tomarev, 2018), as summarized in Table 2.…”

“…In addition, MSCs have a paracrine effect that promotes immunomodulation as well as antiapoptotic and anti-oxidative effects, which can be helpful for treating neuromuscular pains (van Buul et al, 2014) and many other diseases (de Witte et al, 2018;Francois et al, 2013;Khubutiya, Vagabov, Temnov, & Sklifas, 2014). MSCs are also being investigated for their therapeutic potential to treat degenerative diseases and disorders such as Parkinson's disease (PD; Jamali, Ma Hattab, Amman, & Awidi, 2018; H. Kim, Lee, et al, 2018), Alzheimer's disease (AD; Cui et al, 2017;Han et al, 2018), amyotrophic lateral sclerosis (Bonafede & Mariotti, 2017), multiple sclerosis (MS; Harris et al, 2018; Nasri Ahn et al, 2015;Beeravolu et al, 2018;Perez-Cruet et al, 2018), retinal degenerative disease (RDD; Y. Wang, Zhang, Shen, Zhang, & Gu, 2018;, myocardial infarction (X. Q.…”