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Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop (2022)

Chapter: 8 Harnessing the Immune System to Improve Patient Outcomes

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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
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8

Harnessing the Immune System to Improve Patient Outcomes

Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×

The objective of the sixth and final session of the workshop was to explore areas of clinical therapeutic need amenable to becoming clinical trial candidates. Candidates of particular interest are those that demonstrate proof of principle of a specific therapeutic for clinical indication and that address the immune system’s role in improving tissue regeneration. Richard McFarland, chief regulatory officer at the Advanced Regenerative Manufacturing Institute, moderated the session.

FINAL PANEL DISCUSSION

Key Challenges and Opportunities for Regenerative Medicine as Offered by the Panelists

To begin the discussion, McFarland noted the aspirational goals of the session, and he asked the panelists to share key challenges and opportunities in their areas of expertise for the field of regenerative medicine. Sherilyn George-Clinton from Multiple Sclerosis: You Are Not Alone remarked that patient communication is both a challenge and an opportunity because low levels of health literacy create space for misunderstanding. At the same time, an opportunity lies in generating better understanding within the patient population, she suggested. Thomas Wynn, vice president of discovery at Pfizer, replied that much of his career has focused on understanding the mechanisms of fibrosis. Attempting to reverse disease and regenerate tissue in a patient with severe fibrosis, and chronic diseases in general, is a major challenge; therefore, one opportunity is developing a deeper understanding of the regenerative mechanisms of the immune system that can be harnessed to address chronic fibrosis, he said. Inflammation resolution is needed to stop the progression of fibrosis, and reversing excess extracellular

Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×

matrix deposition will require leveraging the immune system, Wynn added. The macrophage may be one of the key cell types in this process due to the ability to produce enzymes that degrade collagen. Wynn expressed his interest in harnessing those mechanisms as an opportunity to reverse fibrosis and restore tissue homeostasis and to better understand how fibrosis impedes regeneration.

A rich area of opportunity lies at the convergence of “domain expertise” in mass spectrometry profiling, metabolomics, and regenerative medicine, said Edward Botchwey, an associate professor in the Department of Biomedical Engineering at the Georgia Institute of Technology. An example of the power of this convergence is the discovery by Charles Serhan, who spoke in an earlier session of the workshop, that bioactive lipids are responsible for active resolution of inflammation. In addition, accessible methods of profiling and modeling injuries could help the field of regenerative engineering effectively leverage endogenous mechanisms of resolution and repair, he suggested. Botchwey and his team have shown through mouse experiments that individual metabolites, such as sphingosine-1-phosphate and leukotriene B4, become elevated at the threshold between muscle injuries that heal successfully and those that yield increased fat and fibrous tissue. Development of effective therapeutic interventions depends on greater understanding of bioactive species and the local mechanisms of their production, degradation, and conversion, said Botchwey. Furthermore, profiling in model systems can improve understanding of the influence of sex, ancestry, and specific injury parameters on repair and regeneration. Perhaps metabolic and immunological signatures could then be used to tailor therapeutics to effectively harness endogenous mechanisms of regeneration, he added.

The key challenge for regenerative medicine and cell therapy is access to medicine, said Sonja Schrepfer, head of the Hypoimmune Platform at Sana Biotechnology. Autologous therapies demonstrate that cell therapy can be effective, and they provide treatment opportunities in both oncology and regenerative medicine. Still, the ability to provide cell therapy to any person, anywhere, at any time is challenging, she said. For instance, specialized allogeneic transplants require overcoming the immunological barrier. However, access to these therapies necessitates distribution of a well-characterized cell product to centers in numerous geographic locations, so off-the-shelf approaches represent a key opportunity, Schrepfer suggested. The ability to provide an off-the-shelf transplant to anyone who needs the therapy will “open the door for regenerative medicine in the future,” she added.

The greatest challenge from a preclinical perspective is adequately assessing the safety of regenerative medicine products prior to first-in-human

Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×

studies, said Danielle Brooks of the Office of Tissues and Advanced Therapies in the U.S. Food and Drug Administration (FDA) Center for Biologics Evaluation and Research. The human immune response to products tested with existing in vitro and in vivo animal models can be difficult to predict. The biggest opportunities in regenerative medicine lie in collaborative workshops, similar to this one hosted by the Forum on Regenerative Medicine, with discussions between disciplines to share novel methods. In addition, early engagement and discussions with the FDA to create multipronged approaches to preclinical development and effectively move products into human trials are helpful and a key opportunity, she said.

The emerging area of initiating immune response by nonmicrobial mechanisms offers great opportunity for discovery, said Jennifer Elisseeff, Morton Goldberg Professor of Ophthalmology and Biomedical Engineering at Johns Hopkins University. Convergence of the fields of autoimmunity, transplants, rejection and tolerance, foreign body response, oncology, and regeneration could lead to complementary discoveries in the immune system. The heterogeneity of patients presents a challenge, but big data could be leveraged to develop immune system therapies that account for the influence of personal history of infections, trauma, exposure, and microbiome on the immune state, Elisseeff said. Biologists, computational scientists, and engineers could work together to build technology to support these efforts, she remarked.

Patient Perspective on Regenerative Therapeutics

Reflecting on the heterogeneity of patients, George-Clinton said that it is common for members of the multiple sclerosis (MS) community to take prescribed immunomodulators and immunosuppressants. The ability to regenerate nerve cells and myelin cells would be of utmost interest to MS patients. Since many people with MS have multiple autoimmune disorders, the notion that the power of the immune system could be harnessed for good and directed toward improving quality of life is exciting, she added. McFarland emphasized the importance of the patient experience in translating science to cures, noting that scientists can become enthralled with the science and lose sight of the patient experience.

Possible Roles of Healing and the Immune System in Regenerative Medicine

McFarland asked the panelists about opportunities on the horizon to harness the immune system to improve tissue regeneration and patient experience. Fibrosis has a role in healing; when the body responds to a cut with fibrosis, it prevents harmful bacteria from entering the injury,

Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×

said Wynn. However, over time fibrosis can be destructive to organs. He and his team are working to slow the progression of harmful fibrosis that impairs organ function, particularly in the lung, muscle, and other tissues. The aim of effectively treating fibrosis can be viewed as three increasingly challenging goals, the first of which involves slowing the progression of the condition, Wynn described. Certain types of fibrosis can be lethal, such as idiopathic pulmonary fibrosis; patients with this progressive disease often die within three to five years of diagnosis. Therefore, slowing the progression of the disease could have significant benefit for patients, he said. A few medicines are able to slow the progression to an extent, but they do not stop it, Wynn noted. The ability to identify the mechanisms driving pathological fibrosis could lead to improvements in slowing its progression. The next goal in treating fibrosis is to reverse scarred tissue; regeneration holds the promise of one day being able to restore normal tissue integrity and architecture. The third objective centers on the ultimate goal of being able to regrow an entirely new organ to replace one that can no longer be repaired. The current focus of therapeutic development is the first stage, slowing progression of fibrosis, said Wynn.

To highlight other promising opportunities, Elisseeff drew an analogy between developments in the cancer immunology field and in regenerative medicine. Initial cancer therapies targeted killing cancer cells, and the field is now working on therapies that use the body’s immune system to fight cancer. Similarly, regenerative therapies focused on stem cells and tissue-specific cells, but the field can now also consider methods to create an environment that enables cells to function as intended. For instance, fibrosis can build tissues or it can be pathological; advancements could arise from differentiating those regenerative versus pathological responses, she noted. Although the connection between the immune system and the stroma is currently center stage, the interaction between the immune system and senescence is an exciting area for exploration, added Elisseeff. Finally, academic–industry partnerships could also serve an important role to move promising therapies to the clinic, she said.

Botchwey remarked on the value of converging knowledge and tools from various fields and diverse perspectives, as the Forum on Regenerative Medicine has done with this workshop. Convening is one way to share important advances in manipulating cellular senescence, harnessing the pathways of inflammation resolution, and understanding functional roles and spatial organizations of immune cells and other cell types. He noted current progress in technologies to interpret single-cell data, in ex vivo model systems to control the arrangement of cells in three dimensions, and in engineering biomaterials to present biomolecules to immune cells that alter their function. By bringing these individual areas together more often, new technologies can become more readily available to researchers engaged

Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×

in discovery, noted Botchwey. Eventually, integration of model systems and approaches can lead to discoveries that otherwise would not have transpired. The virtual world may increase the frequency of such interactions, he added.

Safety Considerations for Complex Therapeutics

A participant asked how the mechanisms of these complex therapeutic options can be fully understood and how such complicated therapies can meet safety and efficacy guidelines, such as those of the FDA. Botchwey emphasized the importance of good experimental models. For example, mouse injury models have shown that an injury of one size heals, whereas an injury of another size does not, with factors like age and sex controlled. Although the result is not yet completely understood, such models capture as much biological complexity as possible in order to research a question thoroughly. In general, exploration that casts a wide net and involves collaboration with other researchers with valuable expertise may yield new therapeutic discoveries, he said.

McFarland asked Schrepfer to address how the participant’s question about safety and efficacy applies to engineering allogeneic donor cells for acceptance by the host immune system. Schrepfer outlined two approaches to encouraging acceptance of transplanted allogeneic cells. The first involves genetically engineering cells to become hypoimmune, meaning that they have been modified to evade recognition by the immune system after transplantation. One benefit of this strategy is that it is stable for the patient, assuming that safe genetic engineering ensures stable cells that will not be recognized by the immune system, she posited. The second approach involves inducing tolerance such that the immune system of the recipient is “educated” to tolerate the transplanted cells. The two approaches are quite different—each involving pros and cons—and the immune status of each individual patient should be considered in determining the best approach, Schrepfer suggested. Considering autoimmune patients as an example, immune evasion may be easier to achieve overall because evasion does not rely on the status of the immune system of the recipient, she said. Both concepts are equally important, and exploring them simultaneously will aid in optimizing methods for cellular transplantation to benefit patients.

Given that transplanted therapeutic cells should be not only shielded from the immune system but also able to replicate, McFarland asked Schrepfer whether there is a risk of oncology carcinogenesis and how risk can be mitigated if the cells are shielded from normal antitumor surveillance. When immune evasion or immune tolerance is in effect, implanted therapeutic cells cannot be controlled using the immune system. Therefore, other methods of controlling cells would be useful, Schrepfer said. Including

Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×

methods like engineered kill switches, various approaches that are disease specific and possibly patient specific could be developed. This risk is important to consider when creating immune evasion or immune tolerance strategies for allogeneic approaches, and interdisciplinary collaboration and a possible future workshop could help address it, Schrepfer added.

McFarland asked Brooks about nonclinical tools that can improve success in translating approaches from the lab to the clinic. Brooks replied that regenerative medicine products and their responses in human subjects are complex. Rather than make generalized recommendations, the FDA works closely with sponsors from academia and industry to determine the best individual approach for a specific regenerative medicine product. Integrating multiple tools and approaches can help researchers gain a comprehensive view of the product, she said. Researchers may communicate with the FDA early in the development process in order to incorporate feedback into their research efforts, Brooks said. McFarland added that developers could ask themselves questions such as the one that he posed to Schrepfer about carcinogenesis. Asking such questions enables generation of evidence that the FDA uses to inform the benefit–risk assessment conducted with each submission, McFarland said. This approach creates a joint responsibility between the FDA and sponsors to consider not only the potential benefits of regenerative medicine products but also the potential risks. Furthermore, the data produced to answer these questions are likely to support both risk mitigation and the product’s benefits, he said. The potential risks to the subject are the FDA’s essential concern, and data on what is known and unknown about the response a product will generate in the host environment enable the agency to make the risk–benefit determination, said Brooks. She intends to debrief her team at the FDA on new approaches in use and products shared during the workshop that could potentially enter clinical trials in coming years.

Emerging Areas in Regenerative Medicine Discussed by Individual Speakers

The field of regenerative medicine requires prolonged focus, said Wynn, noting that after three decades of work on the mechanisms of fibrosis, therapeutics that effectively treat and slow the progression of severe outcomes of fibrotic disease have not been forthcoming. In addition, the emerging area of understanding how the senescence-associated secretory phenotype—referred to as SASP—drives the process of senescence merits attention, he said. Botchwey remarked that interest in the effects of sex on regeneration and aging can be expanded to include consideration of race and health disparities. The fields of immunology and regenerative medicine may engage societal problems—that were brought to the nation’s attention again in

Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×

2020 by the death of George Floyd—through research that provides insight into the variability of patient outcomes based on ancestry, Botchwey said. Similarly, Elisseeff highlighted the role of sex differences in regenerative medicine, noting that sex differences emerge when examining COVID-19 disease severity and vaccine responses. Genetic associations with certain human leukocyte antigens and the propensity for autoimmune disease should also be considered. In addition, Elisseeff noted her excitement about the potential for the field of regenerative medicine to positively affect patients. To do so, the complex science involved in regenerative therapies might be simplified and translated into manufactured products that can be delivered in a cost effective and impactful way, she said. Lastly, the immune system is often seen as a barrier that must be overcome for a successful transplant, Schrepfer stated, but the immune system holds power that can be utilized to prevent and reverse disease.

Evolution of the Field of Tissue Regeneration

McFarland concluded the session with a reflection on the evolution of tissue engineering. While completing his Ph.D., McFarland was temporarily distracted from his thesis work by the synopsis of a workshop about tissue engineering (Skalak and Fox, 1988). A professor told him to focus on his thesis, because if the content of the workshop was important, it would still be there after his thesis was complete. Indeed, this area of research is still active three decades later. Even in the early 2000s, as an immunologist and reviewer for the FDA conducting pharmacology and toxicology reviews, the immune system was either deemed a problem or not discussed, he noted. At that time, Carl June, a pioneer in chimeric antigen receptor T-cell therapy, talked about the potential to enhance the capabilities of the immune system using tumor-infiltrating lymphocytes, but the promise was not fully realized. Over 15 years later, Memorial Sloan Kettering and the National Institutes of Health achieved this goal of eliciting a positive immune response. In contrast to earlier approaches that emphasized sterility, current discussion about biocompatibility centers on modifying the environment to be conducive to regeneration of tissues and organs, he said. McFarland concluded by discussing his vision for the future and highlighting the potential for regenerative medicine to have far-reaching positive impact.

REFLECTIONS ON THE WORKSHOP

Reflections on the workshop’s themes were provided by Kimberlee Potter, scientific program manager for the Biomedical Laboratory Research and Development Service at the U.S. Department of Veterans Affairs Office of Research and Development, and Nadya Lumelsky, chief of the Integrative

Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×

Biology and Infectious Diseases Branch and director of the Tissue Engineering and Regenerative Medicine Research Program at the National Institute of Dental and Craniofacial Research.

In her concluding remarks, Lumelsky commended the interdisciplinary nature of the workshop and emphasized the value of bringing together the fields of exogenous cell manipulation and endogenous host environment manipulation. The workshop highlighted the emerging view that the immune system has many functions beyond defense from pathogens, as described by Medzhitov, Elisseeff, Moore, and others. Lumelsky emphasized that the absence of inflammation is not the same as inflammation resolution, as Serhan had observed in an earlier session. In fact, many investigators have shown that inflammation suppression can have deleterious effects for tissue regeneration, as optimal resolution of inflammation is critical for tissue regeneration, Lumelsky explained. Throughout the workshop, speakers provided examples of how the immune system could be modulated and its power harnessed to improve patient outcomes (see Box 8-1).

Tissue or Cell-based Transplantation and Exogenous Manipulation of Donor Cells

Presenting lessons from organ transplant immunology that might apply to regenerative medicine, Sykes outlined different transplantation protocols, efforts to move toward immune tolerance, and how various techniques access different immune mechanisms. By reducing the need for immunosuppressive drugs and therefore the devastating side effects they can cause, induction of immune tolerance could prove beneficial to patients because they can alleviate injection concerns as well as leave the immune system intact to combat infections, Potter summarized. Adding to the discussion, Schrepfer, Le Blanc, and Valamehr shared various strategies to evade immune detection or induce immune tolerance in the host to increase acceptance of exogenous cell therapies. Finally, Sadelain discussed anti-cancer CAR T immunotherapies featuring engineered T cells, which he described as “living drugs.” Lumelsky reiterated that CAR T therapies may be a future tool for removing senescent cells and modulating tissue regeneration.

Endogenous Mechanisms of Repair and their Modulation

The workshop also featured approaches that do not require exogenous cell injection; rather, the strategies manipulate endogenous modulators of cell processes to repair or build new tissue, Lumelsky summarized. For example, Blau discussed the activity of prostaglandin E2, an inflammatory mediator, in augmenting skeletal muscle and preventing sarcopenia, an age-related muscle wasting condition. Hajishengallis shared how a secreted

Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×

protein called DEL-1 promotes inflammation resolution and tissue regeneration in periodontitis. Lumelsky also highlighted the importance of inflammation resolution and the pro-resolving mediators that Serhan pioneered.

Several of these key mediators exhibit altered expression in aging, and the role of senescent cells in disease and aging was discussed by Kirkland. He explained that aging involves interrelated fundamental processes, and interventions that target one process tend to also affect other processes of aging. Thus, senolytic agents could possibly affect pleiotropic aging in various directions, preventing and delaying age-related conditions and diseases, Lumelsky summarized. Lumelsky expressed her hope that someday many conditions will be amenable to therapies that manipulate endogenous modulators of cell regeneration, cell degeneration, and aging and that exogenous cell injection may no longer be necessary for building new tissues.

Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×

Tools to Investigate and Modulate the Immune System

The workshop also included examples of tools and concepts to monitor, investigate, and optimize the immune environment. For instance, Medzhitov introduced concepts of tissue homeostasis and division of labor among different cell types. These concepts could serve as models for ideas being developed in tissue regeneration, suggested Potter. Moreover, systems biology approaches may enable researchers to better understand the complexities of biological tissues. Nolan provided an overview of the multiplexing imaging tool CODEX and how the data from it can be used to define cellular neighborhoods. Nolan emphasized the importance of interfaces between cellular neighborhoods, and results indicate that the local biology of these neighborhoods may have prognostic value for diagnosis and

Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×

clinical treatment. Nolan’s concept of cellular neighborhoods resonates with Medzhitov’s discussion of the functional and structural role of cellular units within tissues, Lumelsky noted.

Biomaterials can be used to model the immune microenvironment to better understand the immune response in disease and wound healing, as presented by Moore, Elisseeff, and Sadtler. Using biomaterials, Moore and her team modeled immune cell mediation in wound healing and profiled the B-cell responses to better understand variability in wound healing. Elisseeff described the tissue microenvironment as an intervention target and highlighted the growing role of big data in this period of discovery. The development of biomaterials with intentionally designed functions may enable researchers and physicians to encourage desired immune responses, Lumelsky summarized. Sadtler had also said that rational design for creating anti-fibrotic and pro-healing biomaterials depends on understanding the fundamental biology. Given their ability to activate biomolecules, these biomaterials could be especially useful; furthermore, the capacity to modulate spatiotemporal components of the niche could augment the effectiveness of these biomaterials, Lumelsky commented.

Imagining the Future of Regenerative Medicine

Reiterating an idea proposed by Jenq, who described how variability in human data can be used to generate new hypotheses, Potter emphasized the importance of reverse engineering hypotheses. Sadtler also highlighted the potential value of integrative, iterative approaches that apply preclinical and quantitative modeling data to clinical therapeutics. Iterative hypothesis generation that incorporates “going from bench to bedside and back to bench” has potential to benefit patients while also enriching foundational knowledge about the role of the immune system in improving tissue regeneration, Lumelsky reflected.

Lumelsky said that the integration of different modalities and therapies emerged as a theme throughout the interdisciplinary workshop, summarizing points made by Kirkland, Elisseeff, Botchwey, and others (see Box 8-1). Future immunotherapies will likely include combination therapies that promote tissue regeneration while inhibiting fibrosis, she said. Combining regenerative medicine, immunology, and biomaterial design, the field of regenerative immunology has the potential to both promote endogenous tissue regeneration and affect the survival and regeneration of exogenous cell-based therapies, Lumelsky remarked in response to Elisseeff’s work.

Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×

Final Thoughts

Despite the challenges presented by the immune system, the many scientific and therapeutic opportunities for regenerative medicine are exciting and could benefit patients in the near future; indeed, “all challenges are connected to an opportunity,” Elisseeff said. The field of regenerative medicine is evolving, and new regenerative immunotherapies can be created through interdisciplinary collaboration to further the goal of helping patients, she said. In this era, big data and collaboration across sciences will be important in achieving the creation of economically feasible, curative therapies that can be distributed to diverse populations, said McFarland. He added that this can be carried out in a way that decreases the disparity that has been inherent in clinical services. Importantly, this field offers the opportunity of moving beyond treatments to cures, McFarland said.

Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×

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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×
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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×
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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×
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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×
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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
×
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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
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Suggested Citation:"8 Harnessing the Immune System to Improve Patient Outcomes." National Academies of Sciences, Engineering, and Medicine. 2022. Understanding the Role of the Immune System in Improving Tissue Regeneration: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26551.
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The Forum on Regenerative Medicine of the National Academies of Sciences, Engineering, and Medicine convened a two-day virtual public workshop to address knowledge gaps in the understanding of promising approaches to manipulate the immune system and/or the regenerative medicine product to improve outcomes of tissue repair and regeneration in patients. The workshop, titled "Understanding the Role of the Immune System in Improving Tissue Regeneration," explored the role of the immune system in the success or failure of regenerative medicine therapies. Participants considered potential strategies to effectively "prepare" patients' immune systems to accept regenerative therapies and increase the likelihood of successful clinical outcomes and also discussed risks associated with modulating the immune system. This Proceedings of a Workshop highlights the presentations and discussions that occurred during the workshop.

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