Changes in immunological profile of allogeneic mesenchymal stem cells after differentiation: should we be concerned?

Lohan, Paul; Coleman, Cynthia M.; Murphy, Mary; Griffin, Matthew D.; Ritter, Thomas; Ryan, Aideen E.

doi:10.1186/scrt488

Cited by 71 publications

(69 citation statements)

References 57 publications

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“…They also lower the immune rejections, induce immune tolerance, and thus improve the success rate of organ transplantation (26). However, immunogenicity of MSCs may be enhanced due to the differentiation process and transplantation microenvironments (9–14). After differentiation or transplantation, MSCs may elicit immune responses, thus reducing the survival and further differentiation of the cells, and finally hamper the clinical application of MSCs.…”

Section: Discussionmentioning

confidence: 99%

“…Due to their hypo-immunogenicity and immunosuppressive properties (6–8), clinical trials on allogenic MSCs injection in many different acute and chronic diseases have been registered and progressed (). However, MSCs may become immunogenic after differentiation and transplantation to host, due to induction process and the microenvironment of transplanted sites (9–14). In vitro differentiation of rat bone marrow-derived MSCs into muscle cells caused elevated expression of MHC-Ia and MHC-II, and became immunogenic.…”

Section: Introductionmentioning

confidence: 99%

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Immunogenicity of insulin-producing cells derived from human umbilical cord mesenchymal stem cells

Yang

Chen

Ren

et al. 2017

Experimental and Therapeutic Medicine

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Mesenchymal stem cells (MSCs) have been considered as hypo-immunogenic and immunosuppressive. However, a thorough understanding of the immunological properties after MSC differentiation in vitro and in vivo has not been reached. We asked whether it would be immunogenic after differentiation or influenced by the immune microenvironment after transplantation. In different disease models, the immunological changes of MSCs after differentiation greatly varied, with contradicting results. In order to clarify this, we used a modified four-step induction method to induce human umbilical cord MSCs (hUCMSCs) to differentiate into insulin-producing cells (IPCs), and investigate the immunological changes after differentiation and immune reactions after transplantation into diabetic mice. We found that the induced IPCs are hypo-immunogenic, lacking HLA-DR, CD40 and CD80 expression. Of note, we observed immune cell infiltration to peritoneal cavity and left kidney capsule after local transplantation of induced IPCs. This indicated that hUCMSC-derived IPCs maintained hypo-immunogenic in vitro, but became immunogenic after transplanting to the host, possibly due to the changes of immune microenvironment and thereafter immunological enhancement and immune cell infiltration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunogenicity of insulin-producing cells derived from human umbilical cord mesenchymal stem cells

Yang

Chen

Ren

et al. 2017

Experimental and Therapeutic Medicine

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“…In-vitro studies suggest that exposure of MSCs to chondrocytes may induce expression of MSC major histocompatibility complex (MHC) I/II and other costimulatory molecules [96]. …”

Section: Altering Msc Activity Prior To Bone or Cartilage Implantationmentioning

confidence: 99%

Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies

2016

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Adult mesenchymal stem cells (MSCs) represent a subject of intense experimental and biomedical interest. Recently, trophic activities of MSCs have become the topic of a number of revealing studies that span both basic and clinical fields. In this review, we focus on recent investigations that have elucidated trophic mechanisms and shed light on MSC clinical efficacy relevant to musculoskeletal applications. Innate differences due to MSC sourcing may play a role in the clinical utility of isolated MSCs. Pain management, osteochondral, nerve, or blood vessel support by MSCs derived from both autologous and allogeneic sources have been examined. Recent mechanistic insights into the trophic activities of these cells point to ultimate regulation by nitric oxide, nuclear factor-kB, and indoleamine, among other signaling pathways. Classic growth factors and cytokines—such as VEGF, CNTF, GDNF, TGF-β, interleukins (IL-1β, IL-6, and IL-8), and C-C ligands (CCL-2, CCL-5, and CCL-23)—serve as paracrine control molecules secreted or packaged into extracellular vesicles, or exosomes, by MSCs. Recent studies have also implicated signaling by microRNAs contained in MSC-derived exosomes. The response of target cells is further regulated by their microenvironment, involving the extracellular matrix, which may be modified by MSC-produced matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs. Trophic activities of MSCs, either resident or introduced exogenously, are thus intricately controlled, and may be further fine-tuned via implant material modifications. MSCs are actively being investigated for the repair and regeneration of both osteochondral and other musculoskeletal tissues, such as tendon/ligament and meniscus. Future rational and effective MSC-based musculoskeletal therapies will benefit from better mechanistic understanding of MSC trophic activities, for example using analytical “-omics” profiling approaches.

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“…Others have found that immunosuppressive therapy is needed for differentiated MSC to survive and evade infiltrating immune cells (46, 47). This has raised concern for the longevity of allogeneic cells in the donor recipient (48) particularly for therapies where the differentiated cell type is important such as cartilage replacement in OA.…”

Section: Mode Of Action Of Msc Supplementationmentioning

confidence: 99%

Stem Cell Considerations for the Clinician

Hasty

Cho

2016

Physical Medicine and Rehabilitation Clinics of North America

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Summary While there is ample evidence that beneficial results can be obtained from the use of MSC, several questions regarding their use remain to be answered. A better definition is needed for the mechanism/s by which the MSC are eliciting the positive outcome of their use whether it lies in the paracrine factors that are made by the MSC that affect the innate or adaptive immunity or impact the metabolism of resident cells, or their contribution as precursor cells giving rise to more differentiated reparative cells. If paracrine effects are desirable, commercial sources of allogeneic MSC could provide an easily obtainable, well-characterized reagent for the clinician. In their function as reparative cells, the longevity and fate of allogeneic MSC needs to be further evaluated on longer-term basis. The use of autologous cells has both advantages and its own inherent disadvantages involving additional procedures for collection, preparation and characterization of the MSC. It is apparent that a critical number of MSC are necessary for an optimal outcome for implantation. It remains to be determined if tissues such as adipose tissue provide more MSC than bone marrow and if the capability for differentiation is equivalent. A better understanding is also needed for how individual patient factors such as age, sex, drug regimens and co-morbidities influence the MSC population. For many of these questions, preclinical models will be helpful, but the task of evaluating and implementing these findings for orthopaedic patients falls onto the shoulders of clinical researchers. Evaluation of these questions is a daunting, but such a challenge fits the concept of personalized medicine in today’s medicine.

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Changes in immunological profile of allogeneic mesenchymal stem cells after differentiation: should we be concerned?

Cited by 71 publications

References 57 publications

Immunogenicity of insulin-producing cells derived from human umbilical cord mesenchymal stem cells

Immunogenicity of insulin-producing cells derived from human umbilical cord mesenchymal stem cells

Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies

Stem Cell Considerations for the Clinician

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