Therapeutic Use of Mesenchymal Stromal Cells: The Need for Inclusive Characterization Guidelines to Accommodate All Tissue Sources and Species

Following their discovery over 50 years ago, mesenchymal stromal cells (MSCs) have become one of the most studied cellular therapeutic products by both academia and industry due to their regenerative potential and immunomodulatory properties. The promise of MSCs as a therapeutic modality has been demonstrated by preclinical data yet has not translated to consistent, successful clinical trial results in humans. Despite the disparities across the field, MSC shareholders are unified under one common goal—to use MSCs as a therapeutic modality to improve the quality of life for those suffering from a malady in which the standard of care is suboptimal or no longer effective. Currently, there is no Food and Drug Administration (FDA)-approved MSC therapy on the market in the United States although several MSC products have been granted regulatory approval in other countries. In this review, we intend to identify hurdles that are impeding therapeutic progress and discuss strategies that may aid in accomplishing this universal goal of widespread therapeutic use.

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The use of mesenchymal stromal cells in the treatment of coronavirus disease 2019

Journal of Translational Medicine ◽

10.1186/s12967-020-02532-4 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Maurice A. Canham ◽

John D. M. Campbell ◽

Joanne C. Mountford

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Immune Response ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Host Response ◽

Distress Syndrome ◽

Graft Versus Host ◽

Immunomodulatory Properties ◽

Efficacious Vaccine

Abstract More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in over 760,000 deaths worldwide so far. As a result, COVID-19 has changed all our lives as we battle to curtail the spread of the infection in the absence of specific therapies against coronaviruses and in anticipation of a proven safe and efficacious vaccine. Common with previous outbreaks of coronavirus infections, SARS and Middle East respiratory syndrome, COVID-19 can lead to acute respiratory distress syndrome (ARDS) that arises due to an imbalanced immune response. While several repurposed antiviral and host-response drugs are under examination as potential treatments, other novel therapeutics are also being explored to alleviate the effects on critically ill patients. The use of mesenchymal stromal cells (MSCs) for COVID-19 has become an attractive avenue down which almost 70 different clinical trial teams have ventured. Successfully trialled for the treatment of other conditions such as multiple sclerosis, osteoarthritis and graft versus host disease, MSCs possess both regenerative and immunomodulatory properties, the latter of which can be harnessed to reduce the severity and longevity of ARDS in patients under intensive care due to SARS-CoV-2 infection.

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Phenotypic and Immunomodulatory Properties of Equine Cord Blood-Derived Mesenchymal Stromal Cells

PLoS ONE ◽

10.1371/journal.pone.0122954 ◽

2015 ◽

Vol 10 (4) ◽

pp. e0122954 ◽

Cited By ~ 24

Author(s):

Laurence Tessier ◽

Dorothee Bienzle ◽

Lynn B. Williams ◽

Thomas G. Koch

Keyword(s):

Cord Blood ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Immunomodulatory Properties

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A Review of Antimicrobial Activity of Dental Mesenchymal Stromal Cells: Is There Any Potential?

Frontiers in Oral Health ◽

10.3389/froh.2021.832976 ◽

2022 ◽

Vol 2 ◽

Author(s):

Oleh Andrukhov ◽

Alice Blufstein ◽

Christian Behm

Keyword(s):

Vitamin D ◽

Antimicrobial Activity ◽

Antimicrobial Peptides ◽

Mesenchymal Stromal Cells ◽

Immune Cells ◽

Stromal Cells ◽

Multilineage Differentiation ◽

Differentiation Potential ◽

Health Maintenance ◽

Immunomodulatory Properties

Antimicrobial defense is an essential component of host-microbial homeostasis and contributes substantially to oral health maintenance. Dental mesenchymal stromal cells (MSCs) possess multilineage differentiation potential, immunomodulatory properties and play an important role in various processes like regeneration and disease progression. Recent studies show that dental MSCs might also be involved in antibacterial defense. This occurs by producing antimicrobial peptides or attracting professional phagocytic immune cells and modulating their activity. The production of antimicrobial peptides and immunomodulatory abilities of dental MSCs are enhanced by an inflammatory environment and influenced by vitamin D3. Antimicrobial peptides also have anti-inflammatory effects in dental MSCs and improve their differentiation potential. Augmentation of antibacterial efficiency of dental MSCs could broaden their clinical application in dentistry.

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Effect of extracorporeal shock wave therapy on equine umbilical cord blood mesenchymal stromal cells in vitro

10.1101/2020.01.10.901439 ◽

2020 ◽

Author(s):

Ramés Salcedo-Jiménez ◽

Judith Koenig ◽

Olivia Lee ◽

Thomas W.G. Gibson ◽

Pavneesh Madan ◽

...

Keyword(s):

Shock Wave ◽

Mesenchymal Stromal Cells ◽

Umbilical Cord Blood ◽

Stromal Cells ◽

Extracorporeal Shock Wave Therapy ◽

Shock Wave Therapy ◽

Extracorporeal Shock Wave ◽

Immunomodulatory Properties

AbstractExtracorporeal shock wave therapy (ESWT) has been shown to induce different biological effects on a variety of cells, including regulation and stimulation of their function and metabolism. ESWT can promote different biological responses such as proliferation, migration, and regenerations of cells. Recent studies have shown that mesenchymal stromal cells (MSCs) secrete factors that enhance the regeneration of tissues, stimulate proliferation and differentiation of cells and decrease inflammatory and immune-reactions. Clinically, the combination of these two therapies has been used as a treatment for tendon and ligament lesions in horses; however, there is no scientific evidence supporting this combination of therapies in vivo. Therefore, the objectives of the study were to evaluate the effects of ESWT on equine umbilical cord blood mesenchymal stromal cells (CB-MSCs) proliferative, metabolic, migrative, differentiation, and immunomodulatory properties in vitro. Three equine CB-MSC cultures from independent donors were treated using an electrohydraulic shock wave generator attached to a water bath. All experiments were performed as triplicates. Proliferation, viability, migration and immunomodulatory properties of the cells were evaluated. Equine CB-MSCs were induced to evaluate their trilineage differentiation potential. ESWT treated cells had increased metabolic activity, showed positive adipogenic, osteogenic, and chondrogenic differentiation, and showed higher potential for differentiation towards the adipogenic and osteogenic cell fates. ESWT treated cells showed similar immunomodulatory properties to none-ESWT treated cells. Equine CB-MSCs are responsive to ESWT treatment and showed increased metabolic, adipogenic and osteogenic activity, but unaltered immunosuppressive properties. In vivo studies are warranted to determine if synergistic effects occur in the treatment of musculoskeletal injuries if ESWT and equine CB-MSC therapies are combined.

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Therapeutic effect of human umbilical cord-derived multipotent mesenchymal stromal cells in a patient with Crigler–Najjar syndrome type I

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2019-64-4-26-34 ◽

2019 ◽

Vol 64 (4) ◽

pp. 26-34

Author(s):

G. T. Sukhikh ◽

A. V. Degtyareva ◽

D. N. Silachev ◽

K. V. Gorunov ◽

I. V. Dubrovina ◽

...

Keyword(s):

Umbilical Cord ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Multipotent Mesenchymal Stromal Cells ◽

Human Umbilical Cord ◽

Type I ◽

Syndrome Type ◽

Safe Level ◽

Period 2

The article presents the results of intravenous transplantation of allogeneic multipotent mesenchymal stromal cells, derived from a human umbilical cord, to a child with Crigler–Najjarsyndrome type I during the first 2 years of life. The therapy is aimed at reduction of the duration of phototherapy while maintaining a safe level of serum bilirubin.In this study, a five-day-old child with the bilirubin level of 340 µmol/l was treated with phototherapy for 16–18 hours daily in the neonatal period. Then, phototherapy was reduced to 14–16 hours. The level of bilirubin varied from 329 to 407 μmol/l. At the age of 2 months, it was decided to use multipotent mesenchymal stromal cells with a significant decrease in the duration of phototherapy up to 2 hours a day. During the observation period (2 years at the time of writing this article) the child received 6 injections of multipotent mesenchymal stromal cells. A positive effect developed within 4–7 days after administration and persisted for 2–3 months. There were no side effects or complications during and after transplantation.Thus, intravenous transplantation of multipotent mesenchymal stromal cells is an effective treatment of Crigler–Najjar syndrome type I; it reducesthe need for phototherapy,significantly improvesthe quality of life of the patients and prolongstheir life with native liver.

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Patient Attitudes Toward Testicular Prosthesis Placement After Orchiectomy

American Journal of Men s Health ◽

10.1177/1557988319861019 ◽

2019 ◽

Vol 13 (4) ◽

pp. 155798831986101 ◽

Cited By ~ 1

Author(s):

Ashwin Srivatsav ◽

Adithya Balasubramanian ◽

Mohit Butaney ◽

Nannan Thirumavalavan ◽

J. Abram McBride ◽

...

Keyword(s):

Quality Of Life ◽

Standard Of Care ◽

The United States ◽

Patient Attitudes ◽

Psychosocial Burden ◽

Cosmetic Appearance ◽

Self Confidence ◽

Implant Positioning ◽

History Of

Orchiectomy is the standard of care for many testicular conditions. Testicular prosthesis placement (TPP) can mitigate psychosocial burden, restore self-image, and improve quality of life for patients requiring orchiectomy. Limited data exist regarding patient attitudes and counseling on TPP in the United States. The objective of this study was to characterize patient experiences after TPP, rationale for pursuing/declining TPP, and satisfaction levels. Patients with a history of urologic conditions warranting orchiectomy were identified and sent an anonymous survey addressing demographics, pre/post counseling, attitudes toward TPP, satisfaction rates, and postoperative complications. Sixteen percent (76/480) of patients completed the survey. Of these, 50.8% (32/63) undergoing orchiectomy were counseled by their surgeon about TPP, and 22.2% (14/63) received a prosthesis. The most common reasons for declining TPP included lack of concern for cosmetic appearance and lack of counseling. Leading reasons for pursuing TPP included improving self-confidence and cosmetic appearance. Although 71% (10/14) of patients were satisfied with TPP, they did highlight areas for improvement. Twenty percent (2/10) felt their implant was too high, 60% (6/10) felt their implant was too firm, 10% (1/10) endorsed discomfort during sex, and 30% (3/10) felt that TPP did not match their size expectations. Despite these findings, 71% (10/14) reported that they would have TPP again and 79% (11/14) would recommend TPP to others. TPP improves body image and quality of life following orchiectomy. Provider counseling plays an important role in influencing a patient’s decision to undergo TPP. Areas of improvement include implant positioning and more effective replication of testicular consistency.

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Vadadustat, a HIF Prolyl Hydroxylase Inhibitor, Improves Immunomodulatory Properties of Human Mesenchymal Stromal Cells

Cells ◽

10.3390/cells9112396 ◽

2020 ◽

Vol 9 (11) ◽

pp. 2396

Author(s):

Katarzyna Zielniok ◽

Anna Burdzinska ◽

Beata Kaleta ◽

Radoslaw Zagozdzon ◽

Leszek Paczek

Keyword(s):

Real Time ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Real Time Pcr ◽

Mononuclear Cells ◽

Therapeutic Potential ◽

Human Peripheral Blood ◽

Immunomodulatory Activity ◽

Peripheral Blood Mononuclear ◽

Immunomodulatory Properties

The therapeutic potential of mesenchymal stromal cells (MSCs) is largely attributed to their immunomodulatory properties, which can be further improved by hypoxia priming. In this study, we investigated the immunomodulatory properties of MSCs preconditioned with hypoxia-mimetic Vadadustat (AKB-6548, Akebia). Gene expression analysis of immunomodulatory factors was performed by real-time polymerase chain reaction (real-time PCR) on RNA isolated from six human bone-marrow derived MSCs populations preconditioned for 6 h with 40 μM Vadadustat compared to control MSCs. The effect of Vadadustat preconditioning on MSCs secretome was determined using Proteome Profiler and Luminex, while their immunomodulatory activity was assessed by mixed lymphocyte reaction (MLR) and Culturex transwell migration assays. Real-time PCR revealed that Vadadustat downregulated genes related to immune system: IL24, IL1B, CXCL8, PDCD1LG1, PDCD1LG2, HIF1A, CCL2 and IL6, and upregulated IL17RD, CCL28 and LEP. Vadadustat caused a marked decrease in the secretion of IL6 (by 51%), HGF (by 47%), CCL7 (MCP3) (by 42%) and CXCL8 (by 40%). Vadadustat potentiated the inhibitory effect of MSCs on the proliferation of alloactivated human peripheral blood mononuclear cells (PBMCs), and reduced monocytes-enriched PBMCs chemotaxis towards the MSCs secretome. Preconditioning with Vadadustat may constitute a valuable approach to improve the therapeutic properties of MSCs.

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Reparative and Regenerative Effects of Mesenchymal Stromal Cells—Promising Potential for Kidney Transplantation?

International Journal of Molecular Sciences ◽

10.3390/ijms20184614 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4614

Author(s):

Merel Pool ◽

Henri Leuvenink ◽

Cyril Moers

Keyword(s):

Kidney Transplantation ◽

Fracture Healing ◽

Kidney Transplant ◽

Mesenchymal Stromal Cells ◽

Current Literature ◽

Stromal Cells ◽

Wound Care ◽

Transplant Outcome ◽

Immunomodulatory Properties ◽

Kidney Transplantations

Mesenchymal stromal cells (MSCs) possess reparative, regenerative and immunomodulatory properties. The current literature suggests that MSCs could improve kidney transplant outcome via immunomodulation. In many clinical domains, research has also focussed on the regenerative and reparative effects of therapies with MSCs. However, in the field of transplantation, data on this subject remain scarce. This review provides an overview of what is known about the regenerative and reparative effects of MSCs in various fields ranging from wound care to fracture healing and also examines the potential of these promising MSC properties to improve the outcome of kidney transplantations.

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